VEGFR
シグナル伝達経路
研究分野
阻害剤の選択性比較
| カタログ番号 | 製品カタログ | 溶解度(25°C) | ||
|---|---|---|---|---|
| 水 | DMSO | アルコール | ||
| S1040 | Sorafenib (BAY 43-9006) tosylate | 0.01 mg/mL | 127 mg/mL | '<1 mg/mL |
| S1042 | Sunitinib (SU11248) malate | <1 mg/mL | 15 mg/mL | ''<1 mg/mL |
| S1029 | Lenalidomide (CC-5013) | <1 mg/mL | 52 mg/mL | <1 mg/mL |
| S1119 | Cabozantinib (BMS-907351) | <1 mg/mL | 100 mg/mL | <1 mg/mL |
| S1490 | Ponatinib (AP24534) | <1 mg/mL | 30 mg/mL | <1 mg/mL |
| S7647 | Lucitanib (E3810) hydrochloride | 59 mg/mL | 59 mg/mL | '''30 mg/mL |
| S4947 | Regorafenib Hydrochloride | <1 mg/mL | 100 mg/mL | ''<1 mg/mL |
| S2221 | Apatinib (YN968D1) mesylate | <1 mg/mL | 22 mg/mL | ''''<1 mg/mL |
| S5248 | Apatinib | <1 mg/mL | 79 mg/mL | '''10 mg/mL |
| S1005 | Axitinib (AG 013736) | <1 mg/mL | 35 mg/mL | '<1 mg/mL |
| S1111 | Foretinib (GSK1363089) | <1 mg/mL | 100 mg/mL | ''<1 mg/mL |
| S1046 | Vandetanib (ZD6474) | <1 mg/mL | 4 mg/mL | <1 mg/mL |
| S1010 | Nintedanib (BIBF 1120) | <1 mg/mL | 6 mg/mL | 3 mg/mL |
| S1178 | Regorafenib (BAY 73-4506) | <1 mg/mL | 97 mg/mL | '<1 mg/mL |
| S1035 | Pazopanib HCl (GW786034 HCl) | <1 mg/mL | 17 mg/mL | <1 mg/mL |
| S1017 | Cediranib (AZD2171) | <1 mg/mL | 90 mg/mL | <1 mg/mL |
| S1264 | PD173074 | <1 mg/mL | 100 mg/mL | 100 mg/mL |
| S1018 | Dovitinib (TKI-258) | <1 mg/mL | 30 mg/mL | <1 mg/mL |
| S1003 | Linifanib (ABT-869) | <1 mg/mL | 75 mg/mL | <1 mg/mL |
| S1101 | Vatalanib (PTK787) 2HCl | 10 mg/mL | 85 mg/mL | '6 mg/mL |
| S2161 | RAF265 (CHIR-265) | <1 mg/mL | 100 mg/mL | 33 mg/mL |
| S1207 | Tivozanib (AV-951) | <1 mg/mL | 20 mg/mL | <1 mg/mL |
| S1032 | Motesanib Diphosphate (AMG-706) | 19 mg/mL | 100 mg/mL | '<1 mg/mL |
| S1164 | Lenvatinib (E7080) | <1 mg/mL | 40 mg/mL | '<1 mg/mL |
| S1084 | Brivanib (BMS-540215) | <1 mg/mL | 74 mg/mL | 3 mg/mL |
| S1361 | MGCD-265 analog | <1 mg/mL | 104 mg/mL | '<1 mg/mL |
| S1486 | AEE788 (NVP-AEE788) | <1 mg/mL | 88 mg/mL | <1 mg/mL |
| S1181 | ENMD-2076 | 1 mg/mL | 105 mg/mL | <1 mg/mL |
| S1220 | OSI-930 | <1 mg/mL | 89 mg/mL | '3 mg/mL |
| S1171 | CYC116 | <1 mg/mL | 24 mg/mL | <1 mg/mL |
| S1363 | Ki8751 | <1 mg/mL | 47 mg/mL | <1 mg/mL |
| S2231 | Telatinib | <1 mg/mL | 82 mg/mL | 1 mg/mL |
| S2622 | PP121 | <1 mg/mL | 64 mg/mL | 2 mg/mL |
| S3012 | Pazopanib | <1 mg/mL | 87 mg/mL | '<1 mg/mL |
| S1557 | KRN 633 | <1 mg/mL | 9 mg/mL | <1 mg/mL |
| S2842 | SAR131675 | <1 mg/mL | 30 mg/mL | <1 mg/mL |
| S2201 | BMS-794833 | <1 mg/mL | 94 mg/mL | ''<1 mg/mL |
| S7397 | Sorafenib (BAY 43-9006) | <1 mg/mL | 63 mg/mL | ''<1 mg/mL |
| S4001 | Cabozantinib malate (XL184) | <1 mg/mL | 100 mg/mL | '<1 mg/mL |
| S1138 | Brivanib Alaninate (BMS-582664) | <1 mg/mL | 88 mg/mL | '88 mg/mL |
| S2859 | Golvatinib (E7050) | <1 mg/mL | 20 mg/mL | <1 mg/mL |
| S2845 | Semaxanib (SU5416) | <1 mg/mL | 22 mg/mL | 2 mg/mL |
| S2897 | ZM 306416 | <1 mg/mL | 67 mg/mL | <1 mg/mL |
| S2896 | ZM 323881 HCl | <1 mg/mL | 10 mg/mL | <1 mg/mL |
| S2018 | ENMD-2076 L-(+)-Tartaric acid | <1 mg/mL | 100 mg/mL | <1 mg/mL |
| S7057 | LY2874455 | <1 mg/mL | 88 mg/mL | 57 mg/mL |
| S8189 | BAW2881 (NVP-BAW2881) | <1 mg/mL | 84 mg/mL | '20 mg/mL |
| S6520 | WHI-P180 | <1 mg/mL | 59 mg/mL | '<1 mg/mL |
| S0504 | SU14813 | <1 mg/mL | 88 mg/mL | '''''<1 mg/mL |
| S6535 | SU1498 | <1 mg/mL | 78 mg/mL | 78 mg/mL |
| S7667 | SU5402 | <1 mg/mL | 59 mg/mL | <1 mg/mL |
| S8721 | PDGFR inhibitor 1 | <1 mg/mL | 97 mg/mL | '9 mg/mL |
| S7688 | Ki20227 | ˂1 mg/mL | 96 mg/mL | 3 mg/mL |
| S7765 | Dovitinib (TKI258) Lactate | 66 mg/mL | 100 mg/mL | '1 mg/mL |
| S5272 | Toceranib phosphate | 2 mg/mL | 2 mg/mL | '<1 mg/mL |
| S5242 | Cediranib Maleate | <1 mg/mL | 100 mg/mL | <1 mg/mL |
| S8188 | BFH772 | <1 mg/mL | 87 mg/mL | 87 mg/mL |
| S5240 | Lenvatinib (E7080) Mesylate | -1 mg/mL | 39 mg/mL | '''-1 mg/mL |
| S0278 | SU5614 | <1 mg/mL | 10 mg/mL | <1 mg/mL |
| S0290 | SU5204 | <1 mg/mL | 53 mg/mL | '''<1 mg/mL |
| S5667 | Fruquintinib (HMPL-013) | <1 mg/mL | 6 mg/mL | <1 mg/mL |
| S8882 | ODM-203 | <1 mg/mL | 100 mg/mL | <1 mg/mL |
| S8401 | Erdafitinib (JNJ-42756493) | <1 mg/mL | 89 mg/mL | '89 mg/mL |
| S0765 | MAZ51 | <1 mg/mL | 15 mg/mL | <1 mg/mL |
| S6526 | SKLB 610 | <1 mg/mL | 83 mg/mL | 27 mg/mL |
| S7781 | Sunitinib (SU11248) | <1 mg/mL | 25 mg/mL | ''<1 mg/mL |
| S8573 | Sitravatinib (MGCD516) | <1 mg/mL | 100 mg/mL | '100 mg/mL |
| S9621 | Donafenib (Sorafenib D3) | <1 mg/mL | 94 mg/mL | '6 mg/mL |
| S2211 | AG-13958 | <1 mg/mL | 94 mg/mL | '<1 mg/mL |
| S7258 | SKLB1002 | <1 mg/mL | 7 mg/mL | <1 mg/mL |
| S5793 | Motesanib (AMG-706) | <1 mg/mL | 75 mg/mL | 8 mg/mL |
| S6870 | Ningetinib | <1 mg/mL | 20 mg/mL | '<1 mg/mL |
| S6843 | X-82 (Vorolanib) | ˂1 mg/mL | 89 mg/mL | '5 mg/mL |
| S0377 | CS-2660 (JNJ-38158471) | <1 mg/mL | 30 mg/mL | '<1 mg/mL |
| S8696 | 2-D08 | <1 mg/mL | 54 mg/mL | '<1 mg/mL |
| S6412 | Altiratinib | <1 mg/mL | 100 mg/mL | '<1 mg/mL |
| S6514 | SU5408 | <1 mg/mL | 6 mg/mL | '<1 mg/mL |
| S7003 | AZD2932 | <1 mg/mL | 89 mg/mL | 5 mg/mL |
| S8726 | Anlotinib (AL3818) dihydrochloride | 96 mg/mL | 96 mg/mL | '''<1 mg/mL |
| S5234 | Nintedanib Ethanesulfonate Salt | 100 mg/mL | 100 mg/mL | '5 mg/mL |
| S6808 | SU5205 | <1 mg/mL | 48 mg/mL | 3 mg/mL |
| S6809 | SU5214 | <1 mg/mL | 50 mg/mL | <1 mg/mL |
| S5077 | Regorafenib (BAY-734506) Monohydrate | -1 mg/mL | 100 mg/mL | '''-1 mg/mL |
| S2366 | Taxifolin (Dihydroquercetin) | <1 mg/mL | 60 mg/mL | 60 mg/mL |
| S0487 | Sulfatinib | ˂1 mg/mL | 96 mg/mL | '˂1 mg/mL |
| S2431 | TMTD (Tetramethylthiuram disulfide) | <1 mg/mL | 48 mg/mL | <1 mg/mL |
亜型選択性的な製品
VEGFR製品
| 製品コード | 製品説明 | 文献中Selleckの製品使用例 | お客様のフィードバック |
|---|---|---|---|
| S1040 |
Sorafenib (BAY 43-9006) tosylateSorafenib (BAY 43-9006) tosylate is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib Tosylate inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib Tosylate induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity. |
Inhibition of breast cancer cell growth using sorafenib. MCF-7 breast cancer cells were treated with increasing concentrations of sorafenib for 5 days. Cell number was measured using a colorimetric growth assay (crystal violet stain) and expressed relative to DMSO treated control cells. |
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| S1042 |
Sunitinib (SU11248) malateSunitinib (SU11248) malate is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM in cell-free assays, and also inhibits c-Kit. Sunitinib Malate effectively inhibits autophosphorylation of Ire1α. Sunitinib Malate increases both death receptor and mitochondrial-dependent apoptosis. |
Autophagy inhibition blocks the antiproliferative effects of sunitinib and sorafenib but not AZD6244. Medullary thyroid cancer–1.1 (MTC-1.1) and TT cells were transfected transiently with scrambled or autophagy protein 5 (Atg-5) small inter fering RNA. After transfection, cells with and without Atg-5 knockdown were exposed to sunitinib (50 nM), sorafenib (10 nM), and AZD6244 (30 nM) for 48 hours. Treated cells were subjected to a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium proliferation assay. Similar experiments were repeated 3 times. Histograms represent the relative percent of OD490 nM absorbance. The asterisk indicates significance versus scrambled small inter fering RNA–treated control ( P < .05). All data are relative multiples of expression compared to untreated cells. The data are representative of 3 experiments and are expressed as the mean ± the standard error. |
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| S1029 |
Lenalidomide (CC-5013)Lenalidomide (CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM in PBMCs. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide promotes cleaved caspase-3 expression and inhibit VEGF expression and induces apoptosis. |
Effect of lenalidomide treatment (50 mg/kg/day, p.o. for 3 days) on expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Fas, Fas ligand (FasL), and cleaved caspase-3 in myocardium from lean and ob/ob mice. (a) Representative gel blots of TNF-α, IL-6, Fas, FasL, cleaved caspase-3 and α-Tubulin (as loading control) using specific antibodies. (b) TNF-α. |
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| S1119 |
Cabozantinib (BMS-907351)Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway. |
Effects of AXL inhibitors on induction of pAKT and rescue of pERK following AXL overexpression. R428, 500 nmol/L; XL184, 3 umol/L; XL880, 100 nmol/L; in the presence or absence of 2 umol/L PLX4720. shAXL is a positive control.
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| S1490 |
Ponatinib (AP24534)Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively. Ponatinib (AP24534) inhibits autophagy. |
RCH-ACV cells were treated with ponatinib(50 nM), PCI-32765(50 nM), or BMS-599626(500 nM) over a time course, and whole-cell extracts were subjected to immunoblot analysis for total or phospho-AKT.
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| S7647新 |
Lucitanib (E3810) hydrochlorideLucitanib (E-3810, AL3810) hydrochloride is a dual inhibitor of Vascular endothelial growth factor receptor (VEGFR) and Fibroblast growth factor receptor (FGFR). Lucitanib hydrochloride (E-3810, AL3810) potently and selectively inhibits VEGFR1, VEGFR2, VEGFR3, FGFR1 and FGFR2 with IC50 of 7 nM, 25 nM, 10 nM, 17.5 nM, and 82.5 nM, respectively. |
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| S4947新 |
Regorafenib HydrochlorideRegorafenib (Stivarga, BAY 73-4506) Hydrochloride is a multi-target inhibitor for VEGFR1, Murine VEGFR2/3, PDGFRβ, Kit (c-Kit), RET (c-RET) and Raf-1 with IC50 of 13 nM, 4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively. |
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| S2221 |
Apatinib (YN968D1) mesylateApatinib mesylate (YN968D1, Rivoceranib) is a potent inhibitor of the VEGF signaling pathway with IC50 values of 1 nM, 13 nM, 429 nM and 530 nM for VEGFR-2, Ret (c-Ret), c-Kit and c-Src, respectively. Apatinib mesylate induces both autophagy and apoptosis. |
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| S5248 |
ApatinibApatinib (Rivoceranib, YN968D1) is a potent inhibitor of the VEGF signaling pathway with IC50 values of 1 nM, 13 nM, 429 nM and 530 nM for VEGFR-2, Ret (c-Ret), c-Kit and c-Src, respectively. Apatinib induces both autophagy and apoptosis. |
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| S1005 |
Axitinib (AG 013736)Axitinib (AG 013736) is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM in Porcine aorta endothelial cells, respectively. |
Secondary assay development. The invasive potential of MDA-MB-231 spheroids was measured using modified Boyden chambers coated with Matrigel™. Invading cells were fixed, stained with DAPI, and quantified by fluorescence microscopy using 5 random fields per filter insert in triplicate. U0126, PF2341066, axitinib, and PKC412 inhibited the invasive potential of MDA-MB-231 spheroids by ~90% as compared to untreated spheroids (UT). ***p ≤ 0.001. IGF1R and dasatinib displayed no statistical difference as compared to UT MDA-MB-231 spheroids. |
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| S1111 |
Foretinib (GSK1363089)Foretinib (GSK1363089, EXEL-2880, XL-880, GSK089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met (c-Met) and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit (c-Kit), PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2. |
c-MET/RON inhibitors restore sensitivity to lapatinib in SK-BR-3-LR cells. Cell growth was determined using the sulforhodamine B assay. The concentration used was 0.1 uM for crizotinib, MGCD-265, XL880, sunitinib, dasatinib, and TAE-684I. The phosphorylation of HER2, AKT and ERK1/2 was determined by Western blotting.
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| S1046 |
Vandetanib (ZD6474)Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM in a cell-free assay. It also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. Not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC50 of 1.1-3.6 μM. No activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC50 above 10 μM. Vandetanib (ZD6474) increases apoptosis and induces autophagy by increasing the level of reactive oxygen species (ROS). |
Vandetanib increases membrane localization of endothelial NO synthase (eNOS). MS1 endothelial cells (ECs) were incubated with 1 μmol/L of vandetanib or matched vehicle (dimethyl sulfoxide [DMSO]). Western blotting analysis showed that vandetanib increases membrane localization of eNOS compared with control (*P<0.04; n=4 per group, studies done in triplicate). These findings show that vandetanib increased the membrane localization of eNOS compared with control. |
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| S1010 |
Nintedanib (BIBF 1120)Nintedanib (BIBF 1120, Intedanib, Vargatef, Ofev) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM in cell-free assays. Phase 3. |
BIBF 1120 inhibition of verapamil-stimulated ABCB1 ATPase activity. ABCB1 ATPase assays were performed according to the instruction of Pgp-Glo™ Assay Systems. Each point represents the mean±SDs for triplated independent determinations |
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| S1178 |
Regorafenib (BAY 73-4506)Regorafenib (BAY 73-4506, Fluoro-Sorafenib, Resihance, Stivarga) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit (c-Kit), RET (c-RET) and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM in cell-free assays, respectively. Regorafenib induces autophagy. |
Hepatoma cells 24 h after plating were treated with vehicle (DMSO), regorafenib (REGO, 0.5 µM), PDE5 inhibitor (sildenafil, 2 µM); or the drugs in combination. 24 hours after treatment cells were isolated and viability determined by trypan blue (n=3, SEM). *P 0.05
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| S1035 |
Pazopanib HCl (GW786034 HCl)Pazopanib HCl (GW786034 HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces autophagic Type II cell death. |
Effect of HDIL-2/TKI on apoptosis of RCC cells. Three RCC cell lines treated with different concentrations of Pazopanib and HDIL-2 and incubated for 48 h. Microscopic images show apoptotic materials 48 h following treatment (arrows show the apoptotic materials in the pazopanib-treated cells).
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| S1017 |
Cediranib (AZD2171)Cediranib (AZD2171, NSC-732208) is a highly potent VEGFR(KDR) inhibitor with IC50 of <1 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM, similar activity against c-Kit and PDGFRβ, 36-, 110-fold and >1000-fold selective more for VEGFR than PDGFR-α, CSF-1R and Flt3 in HUVEC cells. Cediranib (AZD2171) induces autophagic vacuole accumulation. Phase 3. |
Western blots of EZH2 expression in A549, HCC461, and HCC4006 cells upon treatment with different doses of VEGFR-2-inhibitor AZD2171 (0, 5 and 10 nM). AZD2171 decreased the expression of EZH2 in HCC4006 and HCC461 cells expressing VEGFR-2 in a dose-dependent manner but did not do so in A549 cells lacking expression of VEGFR-2.
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| S1264 |
PD173074PD173074 is a potent FGFR1 inhibitor with IC50 of ~25 nM and also inhibits VEGFR2 with IC50 of 100-200 nM in cell-free assays, ~1000-fold selective for FGFR1 than PDGFR and c-Src. PD173074 reduces proliferation and promotes apoptosis in gastric cancer cells. |
FGFR inhibitors block signaling in FGFR2-fusion-expressing cells. Activation of FGFR2 and MAPK by FGFR2-AHCYL1 and its suppression by FGFR inhibitors. Lysates from NIH3T3 cells expressing FGFR2-AHCYL1 or EZR-ROS1 (control) treated with vehicle (DMSO), 0.2 and 1 uM BGJ398, and 0.2 and 1 uM PD173074 were immunoblotted with the relevant antibodies. β-Actin was used as a loading control.
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| S1018 |
Dovitinib (TKI-258)Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4. |
Orthotopic xenografts of HNSCC cell lines (A) SCC-1 and (B) OSC-19 were treated with dovitinib (20 mg/kg/day). In addition, the OSC-19 xenografts were treated with +/ radiation therapy. Marker, mean for triplicate; bars, SE. Statistical significance by unpaired t-test, p < 0.05. |
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| S1003 |
Linifanib (ABT-869)Linifanib (ABT-869, AL39324, RG3635) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR, CSF-1R, Flt-1/3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM/4 nM and 66 nM respectively, mostly effective in mutant kinase-dependent cancer cells (i.e. FLT3). Linifanib (ABT-869) induces autophagy and apoptosis. Phase 3. |
(B and C) KMCH-1 cells were plated alone (monoculture) or together with PDGF-BB-secreting LX-2 cells (co-culture) in a transwell insert co-culture system (KMCH-1 cells in the bottom wells and LX-2 cells in the inserts; 1:1 ratio) for 2 days. Cells were treated as indicated with vehicle, rhTRAIL (10 ng/ml for 6 h on day 2), rhTRAIL plus imatinib [rhTRAIL:10 ng/ml for 6 h on day 2; Imatinib: 5 μmol/L for 24 h (day2)], or rhTRAIL plus linifanib [rhTRAIL: 10 ng/ml for 6 h on day 2; Linifanib:0.5 μmol/L for 24 h (day2)]. After rhTRAIL treatment for 6 h,KMCH-1 cells were analysed for apoptotic nuclear morphology by DAPI-staining (B) and for DNA fragmentation by transferasemediated dUTP nick end labelling assay (C) with quantification of apoptotic nuclei by fluorescence microscopy. |
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| S1101 |
Vatalanib (PTK787) 2HClVatalanib 2HCl (PTK787, ZK 222584, cpg-79787) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM in a cell-free assay, less potent against VEGFR1/Flt-1, 18-fold against VEGFR3/Flt-4. Phase 3. |
(Aa-Ja) A single row of BTs on the intact fin and stump after 6-14 dot with PTK787 and 4-12 dot with T. Small BTs appear in the fin regenerate after 8 dot with PTK787 and 6 dot with T (Da,Ea). A small BT cluster appears on the regenerate after 14 dot with PTK787 and 12 dot with T (Ga,Ha). (Ab-Jb) After 4 dot with T, BTs develop on the regenerate, stump and intact fin and continue to grow from 6-12 dot. (Jb) After 12 dot, the blood vessel network of T-treated females is similar to that of males. (Ac-Jc) PTK787-treated females do not possess BTs. (Aa-Ja,Ac-Jc) Neo-angiogenesis and regenerative outgrowth are inhibited in all PTK787-treated females. (Ad-Jd) System water controls regenerate normally and do not grow BTs. B.F., brightfield. Fli, fli1a:EGFP (green). KR21 (red) outlines the BTs. White vertical lines indicate the amputation plane. Scale bar: 100 um.
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| S2161 |
RAF265 (CHIR-265)RAF265 (CHIR-265) is a potent selective inhibitor of C-Raf/B-Raf/B-Raf V600E with IC50 of 3-60 nM, and exhibits potent inhibition on VEGFR2 phosphorylation with EC50 of 30 nM in cell-free assays. RAF265 (CHIR-265) induces cell cycle arrest and apoptosis. Phase 2. |
Immunoblots showing levels of phospho-MEK (p-MEK), total MEK (t-MEK), phospho-ERK1/2 (p-ERK1/2) and total ERK1/2 (t-ERK1/2) in A375 cells transduced with a retrovirus expressing BRAFV600E, BRAFV600E/L505H, BRAFV600E/F516G or BRAFV600E/T529N and treated with increasing doses of RAF265. α-tubulin (TUBA) was monitored as a loading control. |
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| S1207 |
Tivozanib (AV-951)Tivozanib (AV-951, KRN-951) is a potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 30 nM/6.5 nM/15 nM, and also inhibits PDGFR and c-Kit, low activity observed against FGFR-1, Flt3, c-Met, EGFR and IGF-1R. Phase 3. |
On-chip angiogenesis assay. Fluorescence imaging of Tg(fli1a:EGFP) embryos at 64 hpf. Transgenic embryos were arrayed and immobilized at 16 hpf and continuously perfused with E3 media containing vehicle control (dimethyl sulfoxide) or selected small-molecule antiangiogenic drugs (Sunitinib and Tivozanib). Right panel: microscopic visualization of patterns of ISV. White arrows: normal ISV growth; blue arrows: partial ISV growth inhibition; and red arrows; complete ISV growth inhibition.
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| S1032 |
Motesanib Diphosphate (AMG-706)Motesanib Diphosphate (AMG-706) is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM, respectively; similar activity against Kit (c-Kit), ~10-fold more selective for VEGFR than PDGFR and Ret. Phase 3. |
Immunofluorescence staining of choroidal neovascularization (CNV) lesions 14 days after laser photocoagulation. Choroidal flat mounts were fluorescently labeled with F-actin-specific marker phalloidin (green channel), endothelial cell marker CD34 (red channel), and nuclear marker DAPI (blue channel). CNV lesions in topical vehicle-treated eye (A, C, E and G) and topical motesanib-treated eye (B, D, F and H). The scale bar represents 100 um.
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| S1164 |
Lenvatinib (E7080)Lenvatinib (E7080) is a multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC50 of 4 nM/5.2 nM, less potent against VEGFR1/Flt-1, ~10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β in cell-free assays. Lenvatinib (E7080) also inhibits FGFR1-4, PDGFR, Kit (c-Kit), RET (c-RET), and shows potent antitumor activities. Phase 3. |
Dot Plot Distribution of Live, Preapoptotic and Apoptotic Cells after Administration of DuP-697 and E7080 Combination.
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| S1084 |
Brivanib (BMS-540215)Brivanib is an ATP-competitive inhibitor against VEGFR2 with IC50 of 25 nM, moderate potency against VEGFR-1 and FGFR-1, but >240-fold against PDGFR-β. Phase 3. |
For MTT assays, cells (2,000 ~ 5,000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of Brivanib by adding 20 μl of 5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution per 100 μl of growth medium. After incubating for 3-4 h at 37°C, the media were removed and 150 µl/well of MTT solvent (either absolute DMSO or isopropanol containing 4 μM HCl and 0.1% Nonidet-40) was added to dissolve the formazan. The absorbance of each well was measured by ELx808 (BioTek, Winooski, VT) or Wallac Victor2 (Perkin-Elmer Life Sciences, Boston, MA) Microplate Reader. Viable cells are presented as percent of control, vehicle-treated cells.
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| S1361 |
MGCD-265 analogMGCD-265 is a potent, multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM, 3 nM/3 nM/4 nM, respectively; also inhibits Ron and Tie2. Phase 1/2. |
c-MET/RON inhibitors restore sensitivity to lapatinib in SK-BR-3-LR cells. The concentration used was 0.1 uM for crizotinib, MGCD-265, XL880, sunitinib, dasatinib, TAE-684, and RON inhibitor I. Columns, means; bars, SEMs (n = 3). The phosphorylation of HER2, AKT and ERK1/2 was determined by Western blotting.
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| S1486 |
AEE788 (NVP-AEE788)AEE788 (NVP-AEE788) is a potent inhibitor of EGFR and HER2/ErbB2 with IC50 of 2 nM and 6 nM, less potent to VEGFR2/KDR, c-Abl, c-Src, and Flt-1, does not inhibit Ins-R, IGF-1R, PKCα and CDK1. Phase 1/2. |
EGFR-SGLT1 interaction is irresponsive to modulators of EGFR’s tyrosine kinase. A: Immunoprecipitation coupled Western blot analysis ofinteractionsbetween EGFR-HA and SGLT1-FlaginHEK293 cells treatedwith EGF or AEE788. EGFR, total EGFR; pEGFR, phosphorylated EGFR; IP, immunoprecipitation; IB, immunoblot. Input, expression levels of indicated exogenous proteinsin HEK293 whole celllysates used for the IP. |
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| S1181 |
ENMD-2076ENMD-2076 has selective activity against Aurora A and Flt3 with IC50 of 14 nM and 1.86 nM, 25-fold selective for Aurora A than over Aurora B and less potent to RET, SRC, NTRK1/TRKA, CSF1R/FMS, VEGFR2/KDR, FGFR and PDGFRα. ENMD-2076 inhibits the growth of a wide range of human solid tumor and hematopoietic cancer cell lines with IC50 from 0.025 to 0.7 μM, which induces apoptosis and G2/M phase arrest. Phase 2. |
Breast cancer cells line MDA-MB-231 were treated with the indicated concentrations of ENMD-2076.
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| S1220 |
OSI-930OSI-930 is a potent inhibitor of Kit (c-Kit), KDR and CSF-1R with IC50 of 80 nM, 9 nM and 15 nM, respectively; also potent to Flt-1, c-Raf and Lck and low activity against PDGFRα/β, Flt-3 and Abl. Phase 1. |
RE-luc2P-HEK293 cells were pretreated with 1uM OSI-930 (green), 20uM TBB (blue), 10uM CKI-7 (purple), or 10uM H-89 (orange) for 16 h and infected with Y. enterocolitica WA or Y. pestis Ind195 at MOI 1 and 20, respectively, for 1 h. Following stimulation with 10 ng/ml TNF-α at 5 h post-infection, luciferase activity was measured 24 h post-infection. Results were determined from two independent experiments performed in triplicate. A"*" denotes that the % NF-κβ inhibition using the inhibitors was significantly different (p<0.05) compared to the no drug control (black). The relative NF-κB inhibition by Yersinia infection was determined as a percentage of luciferase activity in bacteria-infected cells relative to luciferase activity in bacteria-free control cells.
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| S1171 |
CYC116CYC116 is a potent inhibitor of Aurora A/B with Ki of 8.0 nM/9.2 nM, is less potent to VEGFR2 (Ki of 44 nM), with 50-fold greater potency than CDKs, not active against PKA, Akt/PKB, PKC, no effect on GSK-3α/β, CK2, Plk1 and SAPK2A. Phase 1. |
Breast cancer cells line MDA-MB-231 were treated with the indicated concentrations of CYC116.
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| S1363 |
Ki8751Ki8751 is a potent and selective inhibitor of VEGFR2 with IC50 of 0.9 nM, >40-fold selective for VEGFR2 than c-Kit, PDGFRα and FGFR-2, little activity to EGFR, HGFR and InsR. |
Effect of select kinase inhibitors on DF508-CFTR maturation analyzed by immunoblotting. 293MSR-GT cells stably expressing DF508-CFTR were treated with 15 uM kinase inhibitors or 0.3% DMSO (vehicle control), as indicated, grown at 37 °C for 48 h, and the appearance of the mature protein, band C, monitored
by immunoblotting with anti-CFTR antibodies. Band B represents the immature protein. DMSO represents vehicle-alone control, 27 °C represents temperature rescue of F508-CFTR at 27 °C, 37 °C represents untreated DF508-CFTR control, and WT represents WT-CFTR. Top panels depict the anti-CFTR immunoblot and bottom panels depict actin (loading) control. ** represents cellular toxicity.
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| S2231 |
TelatinibTelatinib (BAY 57-9352) is a potent inhibitor of VEGFR2/3, c-Kit and PDGFRα with IC50 of 6 nM/4 nM, 1 nM and 15 nM, respectively. Phase 2. |
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| S2622 |
PP121PP-121 is a multi-targeted inhibitor of PDGFR, Hck, mTOR, VEGFR2, Src and Abl with IC50 of 2 nM, 8 nM, 10 nM, 12 nM, 14 nM and 18 nM, also inhibits DNA-PK with IC50 of 60 nM. |
PP121 induces apoptosis in ATC cells. CAL62 cells were treated with PP121 at the indicated concentrations for 48 h, followed by PI staining. The nuclei were stained with Hoechst and analyzed using a fluorescent microscope. The representative images are shown.
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| S3012 |
PazopanibPazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms/CSF1R with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces cathepsin B activation and autophagy. |
Three RCC cell lines treated with different concentrations of TKI and HDIL-2 and incubated for 48 h. Microscopic images show apoptotic materials 48 h following treatment (arrows show the apoptotic materials in the pazopanib-treated cells).
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| S1557 |
KRN 633KRN 633 is an ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 170 nM/160 nM/125 nM, weakly inhibits PDGFR-α/β and c-Kit, does not block the phosphorylation of FGFR-1, EGFR or c-Met in cell. |
Inhibited migration of hNSCs toward HeLa cells with the treatment of KRN633, a VEGFR2 inhibitor. The cultured hNSCs were treated with KRN633 for 6 h. After that, the transwell migration assay was performed as described above. The number of migrated cells was counted and the results were presented as means ± SD. Magnification,× 200. *P < 0.05 vs. KRN633 non-treated
GESTECs. (A) Migrated HB1.F3.CD cells. (B) Migrated HB1.F3.CD.IFN-β cells.
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| S2842 |
SAR131675SAR131675 is a VEGFR3 inhibitor with IC50/Ki of 23 nM/12 nM in cell-free assays, about 50- and 10-fold more selective for VEGFR3 than VEGFR1/2, little activity against Akt1, CDKs, PLK1, EGFR, IGF-1R, c-Met, Flt2 etc. |
Blockade of IPC-induced ischemic tolerance by the VEGFR-3 inhibitor SAR131675. (A) Representative images of FJ-stained brain sections from sham + SARH (i), sham-IPC + SI + Veh (ii), IPC + SI + Veh (iii) and IPC + SI + SARH (iv) groups. Note that there were more degenerated neurons in the IPC + SI + SARH group receiving SAR131675 of 50 mg/kg as an initial dose than in the IPC + SI + Veh group. Scale bar = 50 μm. (B) The quantitative analysis shows the number of FJ-positive degenerated neurons in the CA1 subregion of the different treatment groups including the IPC + SI + SARL group receiving SAR131675 of 25 mg/kg as an initial dose. Data are presented as the mean ± SEM; # p < 0.05 compared with the sham-IPC + SI + Veh group; *p < 0.05 compared with the IPC + SI + Veh group. (C) Representative images of NeuN immunofluorescence in the sham + SARH (i), sham-IPC + SI + Veh (ii), IPC + SI + Veh (iii) and IPC + SI + SARH (iv) groups. Note that NeuN-immunofluorescence in the IPC + SI + SARH group was reduced compared with the IPC + SI + Veh group. Scale bar = 50 μm. (D) The quantitative analysis shows the number of NeuN-positive intact pyramidal neurons in the CA1 subregion for the different treatment groups. Data are presented as the mean ± SEM; #p < 0.05 compared with the sham-IPC + SI + Veh group; *p < 0.05 compared with the IPC + SI + Veh group. |
|
| S2201 |
BMS-794833BMS-794833 is a potent ATP competitive inhibitor of Met (c-Met)/VEGFR2 with IC50 of 1.7 nM/15 nM, also inhibits Ron, Axl and Flt3 with IC50 of <3 nM; a prodrug of BMS-817378. Phase 1. |
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| S7397 |
Sorafenib (BAY 43-9006)Sorafenib (BAY 43-9006, NSC-724772) is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity. |
Involvement of EV linc-VLDLR in tumor cell responses to chemotherapy. Cells were incubated with sorafenib, camptothecin, or doxorubicin. EVs were obtained after 24 hours, and qRT-PCR was performed for linc-VLDLR. The bars represent the mean ?SEM of the increase in cell viability from 3 independent studies. *, P < 0.05.
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| S4001 |
Cabozantinib malate (XL184)Cabozantinib malate (XL184) is the malate of Cabozantinib, a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret (c-Ret), Kit (c-Kit), Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. Cabozantinib malate (XL184) induces apoptosis. |
Effects of AXL inhibitors on induction of pAKT and rescue of pERK following AXL overexpression. R428, 500 nmol/L; XL184, 3 umol/L; XL880, 100 nmol/L; in the presence or absence of 2 umol/L PLX4720. shAXL is a positive control.
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| S1138 |
Brivanib Alaninate (BMS-582664)Brivanib alaninate (BMS-582664) is the prodrug of BMS-540215, an ATP-competitive inhibitor against VEGFR2 with IC50 of 25 nM. |
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| S2859 |
Golvatinib (E7050)Golvatinib (E7050) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, does not inhibit bFGF-stimulated HUVEC growth (up to 1000 nM). Phase 1/2. |
PC-9/LMC-GR cells (2 × 105 cells/well) were incubated in 6-well plates with various concentrations of gefitinib with or without crizotinib (1 μmol/L) or golvatinib (1 μmol/L) for 1 hour. Cell lysate were obtained and subjected to immunoblotting with antibodies toward the indicated molecules.
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| S2845 |
Semaxanib (SU5416)Semaxanib (SU5416) is a potent and selective VEGFR(Flk-1/KDR) inhibitor with IC50 of 1.23 μM, 20-fold more selective for VEGFR than PDGFRβ, lack of activity against EGFR, InsR and FGFR. Phase 3. |
Injected tumor cells move to the tail via blood vessels. Tg (flil1:egfp) embryos at 20 hpf were treated with 2 μM SU5416 for 1 hr (+SU5416) to inhibit vasculogenesis24; the control fish were treated with 0.02% DMSO for 1 hr (-SU5416). After 1 hr, SU5416 or DMSO was washed out by changing fish media. At 48 hpf, tfRFP-B16 cells were injected into the pericardium cavity of fish. Representative images show that tumor cells moved to the tail in a drug-free larva, while no tumor cells moved to the tail in a drug-treated larva after new vessels were inhibited by SU5416. Insets are enlarged images from each corresponding tip of the tail indicated by white arrows. Dashed white lines mark extravasated tumor cells at 12 hpi. Vessels are green and tumor cells are red. –SU5416, 6 other larvae exhibit similar behaviors; +SU5416, 3 other larvae exhibit similar behaviors. Scale bars, 500 μm. Insets, 100 μm.
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| S2897 |
ZM 306416ZM 306416 (CB 676475) is a VEGFR (Flt and KDR) inhibitor for VEGFR1 with IC50 of 0.33 μM, but also found to inhibit EGFR with IC50 of <10 nM. |
Panels D-F show morphological changes of RBEC cells due to Sema3A treatment. RBECs were fixed after the indicated treatment and stained with phalloidin conjugated with rhodamine (red color) and counter stained with DAPI (blue color). F-actin stress fibres are very clear in untreated cells (D). Sema3A treatment caused disruption of F-actin inside the cells. Densely packed bundles of cortical actin filaments started to appear along cell membranes (arrows) over the course of treatment with Sema3A. Antibodies and inhibitors against receptors of Sema3A were pre-incubated with the cells for 15 min before the addition of Sema3A. Antibodies to VEGFR1 and NRP2 (panel E) and the inhibitor Zm 306416 (selective to VEGFR1, panel F) were effective in ameliorating the effect of Sema3A. Scale bar=20 μm. |
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| S2896 |
ZM 323881 HClZM 323881 is a potent and selective VEGFR2 inhibitor with IC50 of <2 nM, almost no activity on VEGFR1, PDGFRβ, FGFR1, EGFR and ErbB2. |
(A) Fluorescence microscopic analysis of Hoechst 33342 staining of NCIH460 and NCI-H460/MX20 cells. Cells were treated as described in ‘2. Materials and Methods’. Scale bar, 10 μm. (B) Effects of ZM323881 on intracellular accumulation of [3H]-mitoxantrone in NCI-H460 and NCI-H460/MX20 cells. (C) Efflux of [3H]-mitoxantrone in the absence and presence of inhibitors in NCI-H460 cells. (D) Efflux of [3H]-mitoxantrone in the absence and presence of inhibitors in NCI-H460/MX20 cells.
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| S2018 |
ENMD-2076 L-(+)-Tartaric acidENMD-2076 L-(+)-Tartaric acid is the tartaric acid of ENMD-2076, selective activity against Aurora A and Flt3 with IC50 of 14 nM and 1.86 nM, 25-fold more selective for Aurora A than Aurora B and less potent to VEGFR2/KDR and VEGFR3, FGFR1 and FGFR2 and PDGFRα. Phase 2. |
Breast cancer cells line MDA-MB-231 were treated with the indicated concentrations of ENMD-2076.
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| S7057 |
LY2874455LY2874455 is a pan-FGFR inhibitor with IC50 of 2.8 nM, 2.6 nM, 6.4 nM, and 6 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively, and also inhibits VEGFR2 activity with IC50 of 7 nM. Phase 1. |
A: Overall structure of LY2874455/FGFR4 complex. B: The diagram of LY2874455. C: Fo-Fc omit map of LY2874455 in the FGFR4/LY2874455 complex. The electron density is superimposed with the final model. D: The DFG motif conformation of FGFR4. Active ApoFGFR4 DFG-in conformation is shown in blue (PDB: 4QQT); FGFR4/Ponatinib DFG-out conformation is shown in yellow (PDB: 4UXQ); FGFR4/BLU9931 DFG-in conformation is shown in pink (PDB: 4XCU); FGFR4/LY2874455 DFG-in conformation is shown in grey (this work). LY2874455 is highlighted in brown.
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| S8189 |
BAW2881 (NVP-BAW2881)BAW2881 (NVP-BAW2881) is a novel vascular endothelial growth factor (VEGF) receptor tyrosine-kinase inhibitor that potently inhibits VEGFR1-3 at 1.0-4.3 nanomolar (nM) concentrations and inhibits PDGFRβ, c-Kit, and RET (c-RET) at 45-72 nM concentrations. |
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| S6520 |
WHI-P180WHI-P180 is a multi-kinase inhibitor with IC50 values of 4.5 and 66 nM for the human proto-oncogene RET (c-RET) and kinase insert domain receptor (KDR), respectively. |
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| S0504 |
SU14813SU14813 (SU 014813) is a multiple receptor tyrosine kinase inhibitor with IC50 of 50 nM, 2 nM, 4 nM and 15 nM for VEGFR2, VEGFR1, PDGFRβ and Kit (c-Kit). SU14813 exhibits potent antiangiogenic and antitumor activity. |
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| S6543 |
ZD-4190ZD-4190 is a submicromolar inhibitor of VEGF RTK activity in vitro with IC50 values of 29 ± 4 nM and 708 ± 63 nM for KDR and Flt-1, respectively. |
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| S6535 |
SU1498SU1498, a powerful inhibitor of KDR (IC50 = 0.7 μM), stimulates accumulation of phosphorylated ERK1/2 in endothelial cells. |
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| S7667 |
SU5402SU5402 is a potent multi-targeted receptor tyrosine kinase inhibitor with IC50 of 20 nM, 30 nM, and 510 nM for VEGFR2, FGFR1, and PDGF-Rβ, respectively. |
Four FGFR inhibitors, namely PD-173074 (PD-74), PD-166866 (PD-66), SU5402 (SU54) and NVP-BGJ398 (BG-98), inhibit A673, SKNMC, POE, RDES and SKES Ewing cell growth in vitro in a dose-dependent manner, whereas normal cells (IMR90 fibroblasts) remained unaffected. PD-74 proved to be most effective in four out of five Ewing sarcoma cell lines tested. Cells were grown in 10% FBS conditions and cell proliferation was measured after 72 h using a Resazurin assay.
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| S8721 |
PDGFR inhibitor 1PDGFR inhibitor 1 is an orally bioavailable switch pocket control inhibitor of wild-type and mutated forms of Kit (c-Kit) and PDGFR with potential antineoplastic activity. It also inhibits several other kinases, including VEGFR2, TIE2, PDGFR-beta and CSF1R, thereby further inhibiting tumor cell growth. |
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| S7688 |
Ki20227Ki20227 is an orally active and highly selective inhibitor of c-Fms tyrosine kinase(CSF1R) with IC50 of 2 nM, 12 nM, 451 nM and 217 nM for c-Fms, vascular endothelial growth factor receptor-2 (KDR/VEGFR-2), stem cell factor receptor (c-Kit), and platelet-derived growth factor receptor beta (PDGFRβ), respectively. |
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| S7765 |
Dovitinib (TKI258) LactateDovitinib (TKI258, CHIR258) Lactate is the Lactate of Dovitinib, which is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGFR1 and HER2. Phase 4. |
(c) Percent survival for the AGS cancer cell line is shown with FGFR2 inhibitors of varying specificity. (d) The KatoIII diffuse gastric cancer cell line was treated with FGFR2 inhibitors of varying specificity. The Y-axis depicts percent survival versus the X-axis with log concentrations. In all panels, error bars represent standard error of the mean. The difference in percent cell survival between KatoIII and AGS cells was statistically significant (P <0.05) at the three highest concentrations of all drugs, except Brivanib which was only significant at the highest concentration. |
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| S5272 |
Toceranib phosphateToceranib phosphate (Palladia, SU11654), the phosphate salt of toceranib, is a selective inhibitor of the tyrosine kinase activity of several members of the split kinase RTK family, including Flk-1/KDR, PDGFR, and Kit with Ki values of 6 nM and 5 nM for Flk-1/KDR and PDGFRβ, respectively. |
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| S5242 |
Cediranib MaleateCediranib Maleate (AZD-2171) is the maleate salt of Cediranib, which is a potent inhibitor of VEGFR with IC50 of <1 nM and also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM. |
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| S8188 |
BFH772BFH772 is a novel potent oral VEGFR2 inhibitor, targeting VEGFR2 kinase with IC50 of 3 nM. |
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| S5240 |
Lenvatinib (E7080) MesylateLenvatinib Mesylate (E7080) is a synthetic, orally available tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR1-3), fibroblast growth factor receptor (FGFR1-4), platelet-derived growth factor receptor α (PDGFRα), stem cell factor receptor (Kit (c-Kit)), and rearranged during transfection (RET (c-RET)). Lenvatinib Mesylate has potential antineoplastic activity. |
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| S0278 |
SU5614SU5614 (Chloro-SU5416, Chloro-Semaxanib) is a small molecule receptor tyrosine kinases (RTK) inhibitor of VEGFR-2, c-kit, and both wild-type and mutant FLT3. SU5614 reduces cell proliferation and induces apoptosis. |
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| S0290 |
SU5204SU5204, an analogue of SU5025, is a pharmacological inhibitor of VEGFR2. |
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| S5667 |
Fruquintinib (HMPL-013)Fruquintinib (HMPL-013) is a small molecule inhibitor with strong potency and high selectivity against VEGFR family. It inhibits VEGFR 1, 2, 3, with IC50 values of 33 nM, 35 nM and 0.5 nM, respectively and shows only weak inhibition of RET, FGFR-1 and c-kit kinases. |
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| S8882 |
ODM-203ODM-203 is a selective inhibitor of FGFR and VEGFR with ic50s of 11 nM,16 nM,6 nM, 35 nM,26 nM,9 nM,5 nM for recombinant FGFR1, FGFR2, FGFR3,FGFR4, VEGFR1, VEGFR2 and VEGFR3, respectively. |
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| S8401 |
Erdafitinib (JNJ-42756493)Erdafitinib (JNJ-42756493) is a potent and selective orally bioavailable, pan fibroblast growth factor receptor (FGFR) inhibitor with potential antineoplastic activity. Erdafitinib also binds to RET (c-RET), CSF-1R, PDGFR-α/PDGFR-β, FLT4, Kit (c-Kit) and VEGFR-2 and induces cellular apoptosis. |
E, Continuous ERK phosphorylation in FGFR inhibitor resistant cells under 24-hour treatment with 1 μmol/L BGJ398 assessed by immunoblotting. FGFR inhibitors: AZD4547, BGJ398, and JNJ-42756493 |
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| S0765 |
MAZ51MAZ51 is a potent and selective inhibitor of vascular endothelial growth factor receptor (VEGFR)-3 (Flt-4) tyrosine kinase. MAZ51 induces cell rounding and G2/M cell cycle arrest in glioma cells through phosphorylation of Akt/GSK3β and activation of RhoA. MAZ51 inhibits the proliferation and induces the apoptosis of a variety of non-VEGFR-3-expressing tumor cell lines. |
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| S6526 |
SKLB 610SKLB-610 is a multi-target inhibitor of the tyrosine kinases. It is most potent against VEGFR2 and exhibits slightly weaker inhibitor of FGFR2 and PDGFR. |
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| S7781 |
Sunitinib (SU11248)Sunitinib (SU11248) is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit. Sunitinib is also a dose-dependent inhibitor of the autophosphorylation activity of IRE1α. Sunitinib induces autophagy and apoptosis. |
Sunitinib decreases FLT-3 and RET phosphor ylation but increases ERK phosphorylation in a time-dependent manner. H295R and SW13 cells were treated with sunitinib (10 nM) for various time points as indi-cated. Cell lysates were prepared and phospho-FLT-3, RET, and ERK levels were monitored by Western Blot-ting. Re-probing against FLT-3, RET, and ERK was done to ensure equal protein loading. |
|
| S8573 |
Sitravatinib (MGCD516)Sitravatinib (MGCD516, MG-516) is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth, including c-Kit, PDGFRβ, PDGFRα, c-Met, and Axl. |
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| S9621 |
Donafenib (Sorafenib D3)Donafenib (Sorafenib D3, Bay 43-9006 D3, CM-4307) is the deuterium labeled Sorafenib. Sorafenib is a multikinase inhibitor IC50s of 6 nM, 15 nM, 20 nM and 22 nM for Raf-1, mVEGFR-2, mVEGFR-3 and B-RAF, respectively. |
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| S2211 |
AG-13958AG-13958 (AG-013958), a VEGFR tyrosine kinase inhibitor, is in clinical development with ST administration for treatment of choroidal neovascularization associated with age–related macular degeneration (AMD). |
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| S7258 |
SKLB1002SKLB1002 is a potent and ATP-competitive VEGFR2 inhibitor with IC50 of 32 nM. |
Protein expressions of VEGFR2, p-VEGFR2, FAK, p-FAK, ERK, p-ERK and VE-cadherin in HCT116 cells with or without SKLB1002 treatment were determined by western blotting analysis. Representative data of three experiments are shown
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| S5793 |
Motesanib (AMG-706)Motesanib (AMG-706) is an orally bioavailable receptor tyrosine kinase inhibitor with IC50 values of 2 nM, 3 nM, 6 nM, 8 nM, 84 nM, 59 nM for VEGFR1, VEGFR2, VEGFR3, Kit, PDGFR and Ret, respectively. |
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| S6870 |
NingetinibNingetinib (CT-053, DE-120, CT053PTSA) is a potent, orally bioavailable inhibitor of tyrosine kinase with IC50 of 6.7 nM, 1.9 nM and <1.0 nM for c-Met, VEGFR2 and Axl, respectively. Ningetinib exhibits antitumor activity. |
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| S6843 |
X-82 (Vorolanib)X-82 (Vorolanib, CM082) is an oral, multikinase, dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) with antiangiogenic and antineoplastic activities. |
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| S0377 |
CS-2660 (JNJ-38158471)CS-2660 (JNJ-38158471) 是一种耐受性良好的、口服有效的、高选择性的 VEGFR-2 抑制剂，IC50值为40 nM。CS-2660（JNJ-38158471）还抑制紧密相关的酪氨酸激酶，如 RET (c-RET) 和 Kit (c-Kit)，IC50为180 nM和500 nM，但无明显活性 (>1 microM) 针对VEGFR-1和VEGFR-3。 |
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| S8696 |
2-D082-D08 (2',3',4'-trihydroxy flavone) is a cell permeable, mechanistically unique inhibitor of protein sumoylation. It is also inhibits Axl, IRAK4, ROS1, MLK4, GSK3β, RET (c-RET), KDR and PI3Kα with IC50 values of 0.49, 3.9, 5.3, 9.8, 11, 11, 17 and 35 nM respectively in biochemical assays. |
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| S6412 |
AltiratinibAltiratinib (DCC-2701) is a potent single-digit nanomolar inhibitor of TRK, Met (c-Met), TIE2, and VEGFR2 kinases with IC50 vaules of 0.9 nM, 4.6 nM, and 0.8 nM for TRKA, B, and C, respectively. It inhibits Met (c-Met) and Met (c-Met) mutant with IC50 values in the range of 0.3-6 nM. |
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| S4686 |
Vitamin EVitamin E (D-alpha-Tocopherol) is a fat-soluble vitamin with potent antioxidant properties. It is a potent peroxyl radical scavenger and inhibits noncompetitively cyclooxygenase activity in many tissues, also inhibits angiogenesis and tumor dormancy through suppressing vascular endothelial growth factor (VEGF) gene transcription. |
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| S6514 |
SU5408SU5408 (VEGFR2 Kinase Inhibitor I) is a potent and selective inhibitor of VEGFR2 Kinase with IC50 of 70 nM. |
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| S7003 |
AZD2932AZD2932 is a potent and mutil-targeted protein tyrosine kinase inhibitor with IC50 of 8 nM, 4 nM, 7 nM, and 9 nM for VEGFR-2, PDGFRβ, Flt-3, and c-Kit, respectively. |
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| S8726 |
Anlotinib (AL3818) dihydrochlorideAnlotinib (AL3818) is a highly potent and selective VEGFR2 inhibitor with IC50 less than 1 nM. It has broad-spectrum antitumor potential in clinical trials. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation. |
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| S5234 |
Nintedanib Ethanesulfonate SaltNintedanib (Intedanib, BIBF 1120) is a small molecule tyrosine-kinase inhibitor with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β, respectively. |
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| S6808 |
SU5205SU5205 is an inhibitor of VEGF receptor 2 (VEGFR2/FLK-1) with IC50 of 9.6 µM. |
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| S6809 |
SU5214SU5214 is an inhibitor of VEGF receptor 2 (VEGFR2/FLK-1) with IC50 of 14.8 µM and EGFR with IC50 of 36.7 µm, respectively. |
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| S5077 |
Regorafenib (BAY-734506) MonohydrateRegorafenib (BAY-734506, Fluoro-sorafenib, Resihance, Stivarga) Monohydrate is a novel oral multikinase inhibitor with IC50 values of 13, 4.2, 46, 22, 7, 1.5, 2.5, 28, 19 nM for VEGFR1, murine VEGFR2, murine VEGFR3, PDGFR-β, Kit (c-Kit), RET (c-RET), RAF-1, B-RAF and B-RAF(V600E) respectively. |
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| S2366 |
Taxifolin (Dihydroquercetin)Taxifolin, type I inhibitor for VEGFR-2 kinase, is a flavonoid in many plants such as Taxus chinensis, Siberian larch, Cedrus deodara and so on. |
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| S0487 |
SulfatinibSulfatinib (HMPL-012, Sufatinib, Surfatinib) is a potent and highly selective tyrosine kinase inhibitor against VEGFR1, VEGFR2, VEGFR3, FGFR1 and CSF1R with IC50 of 2 nM, 24 nM, 1 nM, 15 nM and 4 nM, respectively. Sulfatinib shows encouraging antitumor activity and manageable toxicities in patients with advanced NETs. |
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| A2006 |
Bevacizumab (anti-VEGF)Bevacizumab (anti-VEGF, Avastin) is a humanized anti-VEGF monoclonal antibody which binds to and neutralizes all human VEGF-A isoforms and bioactive proteolytic fragments, MW:149 KD. |
VEGFA expression in the indicated cells treated with or without bevacizumab or transfected with VEGFA or shVEGFA.
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| A2003 |
Ramucirumab (anti-VEGFR2)Ramucirumab is a monoclonal antibody of the IgG1 class that binds to VEGF-R2 and prevents its activation. The IC50 value for blocking KDR binding to VEGF is 0.8 nM for ramucirumab, MW : 143.6 KD. |
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| S2431 |
TMTD (Tetramethylthiuram disulfide)TMTD (Tetramethylthiuram disulfide) can reduce the growth performance of chickens through decreasing liver index, whereas increasing kidney, cardiac, and spleen index, and induces tibial dyschondrolplasia (TD) by changing the expressions of VEGF, HIF-1α and WNT4. TMTD (Tetramethylthiuram disulfide) is widely used in rubber processing as an ultra accelerator for low-temperature cures and in agriculture as an important pesticide. |
| 製品コード | 製品説明 | 文献中Selleckの製品使用例 | お客様のフィードバック |
|---|---|---|---|
| S1040 |
Sorafenib (BAY 43-9006) tosylateSorafenib (BAY 43-9006) tosylate is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib Tosylate inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib Tosylate induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity. |
Inhibition of breast cancer cell growth using sorafenib. MCF-7 breast cancer cells were treated with increasing concentrations of sorafenib for 5 days. Cell number was measured using a colorimetric growth assay (crystal violet stain) and expressed relative to DMSO treated control cells. |
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| S1042 |
Sunitinib (SU11248) malateSunitinib (SU11248) malate is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM in cell-free assays, and also inhibits c-Kit. Sunitinib Malate effectively inhibits autophosphorylation of Ire1α. Sunitinib Malate increases both death receptor and mitochondrial-dependent apoptosis. |
Autophagy inhibition blocks the antiproliferative effects of sunitinib and sorafenib but not AZD6244. Medullary thyroid cancer–1.1 (MTC-1.1) and TT cells were transfected transiently with scrambled or autophagy protein 5 (Atg-5) small inter fering RNA. After transfection, cells with and without Atg-5 knockdown were exposed to sunitinib (50 nM), sorafenib (10 nM), and AZD6244 (30 nM) for 48 hours. Treated cells were subjected to a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium proliferation assay. Similar experiments were repeated 3 times. Histograms represent the relative percent of OD490 nM absorbance. The asterisk indicates significance versus scrambled small inter fering RNA–treated control ( P < .05). All data are relative multiples of expression compared to untreated cells. The data are representative of 3 experiments and are expressed as the mean ± the standard error. |
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| S1029 |
Lenalidomide (CC-5013)Lenalidomide (CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM in PBMCs. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide promotes cleaved caspase-3 expression and inhibit VEGF expression and induces apoptosis. |
Effect of lenalidomide treatment (50 mg/kg/day, p.o. for 3 days) on expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Fas, Fas ligand (FasL), and cleaved caspase-3 in myocardium from lean and ob/ob mice. (a) Representative gel blots of TNF-α, IL-6, Fas, FasL, cleaved caspase-3 and α-Tubulin (as loading control) using specific antibodies. (b) TNF-α. |
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| S1119 |
Cabozantinib (BMS-907351)Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway. |
Effects of AXL inhibitors on induction of pAKT and rescue of pERK following AXL overexpression. R428, 500 nmol/L; XL184, 3 umol/L; XL880, 100 nmol/L; in the presence or absence of 2 umol/L PLX4720. shAXL is a positive control.
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| S1490 |
Ponatinib (AP24534)Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively. Ponatinib (AP24534) inhibits autophagy. |
RCH-ACV cells were treated with ponatinib(50 nM), PCI-32765(50 nM), or BMS-599626(500 nM) over a time course, and whole-cell extracts were subjected to immunoblot analysis for total or phospho-AKT.
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| S7647新 |
Lucitanib (E3810) hydrochlorideLucitanib (E-3810, AL3810) hydrochloride is a dual inhibitor of Vascular endothelial growth factor receptor (VEGFR) and Fibroblast growth factor receptor (FGFR). Lucitanib hydrochloride (E-3810, AL3810) potently and selectively inhibits VEGFR1, VEGFR2, VEGFR3, FGFR1 and FGFR2 with IC50 of 7 nM, 25 nM, 10 nM, 17.5 nM, and 82.5 nM, respectively. |
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| S4947新 |
Regorafenib HydrochlorideRegorafenib (Stivarga, BAY 73-4506) Hydrochloride is a multi-target inhibitor for VEGFR1, Murine VEGFR2/3, PDGFRβ, Kit (c-Kit), RET (c-RET) and Raf-1 with IC50 of 13 nM, 4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively. |
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| S2221 |
Apatinib (YN968D1) mesylateApatinib mesylate (YN968D1, Rivoceranib) is a potent inhibitor of the VEGF signaling pathway with IC50 values of 1 nM, 13 nM, 429 nM and 530 nM for VEGFR-2, Ret (c-Ret), c-Kit and c-Src, respectively. Apatinib mesylate induces both autophagy and apoptosis. |
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| S5248 |
ApatinibApatinib (Rivoceranib, YN968D1) is a potent inhibitor of the VEGF signaling pathway with IC50 values of 1 nM, 13 nM, 429 nM and 530 nM for VEGFR-2, Ret (c-Ret), c-Kit and c-Src, respectively. Apatinib induces both autophagy and apoptosis. |
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| S1005 |
Axitinib (AG 013736)Axitinib (AG 013736) is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM in Porcine aorta endothelial cells, respectively. |
Secondary assay development. The invasive potential of MDA-MB-231 spheroids was measured using modified Boyden chambers coated with Matrigel™. Invading cells were fixed, stained with DAPI, and quantified by fluorescence microscopy using 5 random fields per filter insert in triplicate. U0126, PF2341066, axitinib, and PKC412 inhibited the invasive potential of MDA-MB-231 spheroids by ~90% as compared to untreated spheroids (UT). ***p ≤ 0.001. IGF1R and dasatinib displayed no statistical difference as compared to UT MDA-MB-231 spheroids. |
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| S1111 |
Foretinib (GSK1363089)Foretinib (GSK1363089, EXEL-2880, XL-880, GSK089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met (c-Met) and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit (c-Kit), PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2. |
c-MET/RON inhibitors restore sensitivity to lapatinib in SK-BR-3-LR cells. Cell growth was determined using the sulforhodamine B assay. The concentration used was 0.1 uM for crizotinib, MGCD-265, XL880, sunitinib, dasatinib, and TAE-684I. The phosphorylation of HER2, AKT and ERK1/2 was determined by Western blotting.
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| S1046 |
Vandetanib (ZD6474)Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM in a cell-free assay. It also inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. Not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC50 of 1.1-3.6 μM. No activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC50 above 10 μM. Vandetanib (ZD6474) increases apoptosis and induces autophagy by increasing the level of reactive oxygen species (ROS). |
Vandetanib increases membrane localization of endothelial NO synthase (eNOS). MS1 endothelial cells (ECs) were incubated with 1 μmol/L of vandetanib or matched vehicle (dimethyl sulfoxide [DMSO]). Western blotting analysis showed that vandetanib increases membrane localization of eNOS compared with control (*P<0.04; n=4 per group, studies done in triplicate). These findings show that vandetanib increased the membrane localization of eNOS compared with control. |
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| S1010 |
Nintedanib (BIBF 1120)Nintedanib (BIBF 1120, Intedanib, Vargatef, Ofev) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM in cell-free assays. Phase 3. |
BIBF 1120 inhibition of verapamil-stimulated ABCB1 ATPase activity. ABCB1 ATPase assays were performed according to the instruction of Pgp-Glo™ Assay Systems. Each point represents the mean±SDs for triplated independent determinations |
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| S1178 |
Regorafenib (BAY 73-4506)Regorafenib (BAY 73-4506, Fluoro-Sorafenib, Resihance, Stivarga) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit (c-Kit), RET (c-RET) and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM in cell-free assays, respectively. Regorafenib induces autophagy. |
Hepatoma cells 24 h after plating were treated with vehicle (DMSO), regorafenib (REGO, 0.5 µM), PDE5 inhibitor (sildenafil, 2 µM); or the drugs in combination. 24 hours after treatment cells were isolated and viability determined by trypan blue (n=3, SEM). *P 0.05
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| S1035 |
Pazopanib HCl (GW786034 HCl)Pazopanib HCl (GW786034 HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces autophagic Type II cell death. |
Effect of HDIL-2/TKI on apoptosis of RCC cells. Three RCC cell lines treated with different concentrations of Pazopanib and HDIL-2 and incubated for 48 h. Microscopic images show apoptotic materials 48 h following treatment (arrows show the apoptotic materials in the pazopanib-treated cells).
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| S1017 |
Cediranib (AZD2171)Cediranib (AZD2171, NSC-732208) is a highly potent VEGFR(KDR) inhibitor with IC50 of <1 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM, similar activity against c-Kit and PDGFRβ, 36-, 110-fold and >1000-fold selective more for VEGFR than PDGFR-α, CSF-1R and Flt3 in HUVEC cells. Cediranib (AZD2171) induces autophagic vacuole accumulation. Phase 3. |
Western blots of EZH2 expression in A549, HCC461, and HCC4006 cells upon treatment with different doses of VEGFR-2-inhibitor AZD2171 (0, 5 and 10 nM). AZD2171 decreased the expression of EZH2 in HCC4006 and HCC461 cells expressing VEGFR-2 in a dose-dependent manner but did not do so in A549 cells lacking expression of VEGFR-2.
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| S1264 |
PD173074PD173074 is a potent FGFR1 inhibitor with IC50 of ~25 nM and also inhibits VEGFR2 with IC50 of 100-200 nM in cell-free assays, ~1000-fold selective for FGFR1 than PDGFR and c-Src. PD173074 reduces proliferation and promotes apoptosis in gastric cancer cells. |
FGFR inhibitors block signaling in FGFR2-fusion-expressing cells. Activation of FGFR2 and MAPK by FGFR2-AHCYL1 and its suppression by FGFR inhibitors. Lysates from NIH3T3 cells expressing FGFR2-AHCYL1 or EZR-ROS1 (control) treated with vehicle (DMSO), 0.2 and 1 uM BGJ398, and 0.2 and 1 uM PD173074 were immunoblotted with the relevant antibodies. β-Actin was used as a loading control.
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| S1018 |
Dovitinib (TKI-258)Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4. |
Orthotopic xenografts of HNSCC cell lines (A) SCC-1 and (B) OSC-19 were treated with dovitinib (20 mg/kg/day). In addition, the OSC-19 xenografts were treated with +/ radiation therapy. Marker, mean for triplicate; bars, SE. Statistical significance by unpaired t-test, p < 0.05. |
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| S1003 |
Linifanib (ABT-869)Linifanib (ABT-869, AL39324, RG3635) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR, CSF-1R, Flt-1/3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM/4 nM and 66 nM respectively, mostly effective in mutant kinase-dependent cancer cells (i.e. FLT3). Linifanib (ABT-869) induces autophagy and apoptosis. Phase 3. |
(B and C) KMCH-1 cells were plated alone (monoculture) or together with PDGF-BB-secreting LX-2 cells (co-culture) in a transwell insert co-culture system (KMCH-1 cells in the bottom wells and LX-2 cells in the inserts; 1:1 ratio) for 2 days. Cells were treated as indicated with vehicle, rhTRAIL (10 ng/ml for 6 h on day 2), rhTRAIL plus imatinib [rhTRAIL:10 ng/ml for 6 h on day 2; Imatinib: 5 μmol/L for 24 h (day2)], or rhTRAIL plus linifanib [rhTRAIL: 10 ng/ml for 6 h on day 2; Linifanib:0.5 μmol/L for 24 h (day2)]. After rhTRAIL treatment for 6 h,KMCH-1 cells were analysed for apoptotic nuclear morphology by DAPI-staining (B) and for DNA fragmentation by transferasemediated dUTP nick end labelling assay (C) with quantification of apoptotic nuclei by fluorescence microscopy. |
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| S1101 |
Vatalanib (PTK787) 2HClVatalanib 2HCl (PTK787, ZK 222584, cpg-79787) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM in a cell-free assay, less potent against VEGFR1/Flt-1, 18-fold against VEGFR3/Flt-4. Phase 3. |
(Aa-Ja) A single row of BTs on the intact fin and stump after 6-14 dot with PTK787 and 4-12 dot with T. Small BTs appear in the fin regenerate after 8 dot with PTK787 and 6 dot with T (Da,Ea). A small BT cluster appears on the regenerate after 14 dot with PTK787 and 12 dot with T (Ga,Ha). (Ab-Jb) After 4 dot with T, BTs develop on the regenerate, stump and intact fin and continue to grow from 6-12 dot. (Jb) After 12 dot, the blood vessel network of T-treated females is similar to that of males. (Ac-Jc) PTK787-treated females do not possess BTs. (Aa-Ja,Ac-Jc) Neo-angiogenesis and regenerative outgrowth are inhibited in all PTK787-treated females. (Ad-Jd) System water controls regenerate normally and do not grow BTs. B.F., brightfield. Fli, fli1a:EGFP (green). KR21 (red) outlines the BTs. White vertical lines indicate the amputation plane. Scale bar: 100 um.
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| S2161 |
RAF265 (CHIR-265)RAF265 (CHIR-265) is a potent selective inhibitor of C-Raf/B-Raf/B-Raf V600E with IC50 of 3-60 nM, and exhibits potent inhibition on VEGFR2 phosphorylation with EC50 of 30 nM in cell-free assays. RAF265 (CHIR-265) induces cell cycle arrest and apoptosis. Phase 2. |
Immunoblots showing levels of phospho-MEK (p-MEK), total MEK (t-MEK), phospho-ERK1/2 (p-ERK1/2) and total ERK1/2 (t-ERK1/2) in A375 cells transduced with a retrovirus expressing BRAFV600E, BRAFV600E/L505H, BRAFV600E/F516G or BRAFV600E/T529N and treated with increasing doses of RAF265. α-tubulin (TUBA) was monitored as a loading control. |
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| S1207 |
Tivozanib (AV-951)Tivozanib (AV-951, KRN-951) is a potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 30 nM/6.5 nM/15 nM, and also inhibits PDGFR and c-Kit, low activity observed against FGFR-1, Flt3, c-Met, EGFR and IGF-1R. Phase 3. |
On-chip angiogenesis assay. Fluorescence imaging of Tg(fli1a:EGFP) embryos at 64 hpf. Transgenic embryos were arrayed and immobilized at 16 hpf and continuously perfused with E3 media containing vehicle control (dimethyl sulfoxide) or selected small-molecule antiangiogenic drugs (Sunitinib and Tivozanib). Right panel: microscopic visualization of patterns of ISV. White arrows: normal ISV growth; blue arrows: partial ISV growth inhibition; and red arrows; complete ISV growth inhibition.
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| S1032 |
Motesanib Diphosphate (AMG-706)Motesanib Diphosphate (AMG-706) is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM, respectively; similar activity against Kit (c-Kit), ~10-fold more selective for VEGFR than PDGFR and Ret. Phase 3. |
Immunofluorescence staining of choroidal neovascularization (CNV) lesions 14 days after laser photocoagulation. Choroidal flat mounts were fluorescently labeled with F-actin-specific marker phalloidin (green channel), endothelial cell marker CD34 (red channel), and nuclear marker DAPI (blue channel). CNV lesions in topical vehicle-treated eye (A, C, E and G) and topical motesanib-treated eye (B, D, F and H). The scale bar represents 100 um.
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| S1164 |
Lenvatinib (E7080)Lenvatinib (E7080) is a multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC50 of 4 nM/5.2 nM, less potent against VEGFR1/Flt-1, ~10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β in cell-free assays. Lenvatinib (E7080) also inhibits FGFR1-4, PDGFR, Kit (c-Kit), RET (c-RET), and shows potent antitumor activities. Phase 3. |
Dot Plot Distribution of Live, Preapoptotic and Apoptotic Cells after Administration of DuP-697 and E7080 Combination.
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| S1084 |
Brivanib (BMS-540215)Brivanib is an ATP-competitive inhibitor against VEGFR2 with IC50 of 25 nM, moderate potency against VEGFR-1 and FGFR-1, but >240-fold against PDGFR-β. Phase 3. |
For MTT assays, cells (2,000 ~ 5,000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of Brivanib by adding 20 μl of 5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution per 100 μl of growth medium. After incubating for 3-4 h at 37°C, the media were removed and 150 µl/well of MTT solvent (either absolute DMSO or isopropanol containing 4 μM HCl and 0.1% Nonidet-40) was added to dissolve the formazan. The absorbance of each well was measured by ELx808 (BioTek, Winooski, VT) or Wallac Victor2 (Perkin-Elmer Life Sciences, Boston, MA) Microplate Reader. Viable cells are presented as percent of control, vehicle-treated cells.
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| S1361 |
MGCD-265 analogMGCD-265 is a potent, multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM, 3 nM/3 nM/4 nM, respectively; also inhibits Ron and Tie2. Phase 1/2. |
c-MET/RON inhibitors restore sensitivity to lapatinib in SK-BR-3-LR cells. The concentration used was 0.1 uM for crizotinib, MGCD-265, XL880, sunitinib, dasatinib, TAE-684, and RON inhibitor I. Columns, means; bars, SEMs (n = 3). The phosphorylation of HER2, AKT and ERK1/2 was determined by Western blotting.
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| S1486 |
AEE788 (NVP-AEE788)AEE788 (NVP-AEE788) is a potent inhibitor of EGFR and HER2/ErbB2 with IC50 of 2 nM and 6 nM, less potent to VEGFR2/KDR, c-Abl, c-Src, and Flt-1, does not inhibit Ins-R, IGF-1R, PKCα and CDK1. Phase 1/2. |
EGFR-SGLT1 interaction is irresponsive to modulators of EGFR’s tyrosine kinase. A: Immunoprecipitation coupled Western blot analysis ofinteractionsbetween EGFR-HA and SGLT1-FlaginHEK293 cells treatedwith EGF or AEE788. EGFR, total EGFR; pEGFR, phosphorylated EGFR; IP, immunoprecipitation; IB, immunoblot. Input, expression levels of indicated exogenous proteinsin HEK293 whole celllysates used for the IP. |
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| S1181 |
ENMD-2076ENMD-2076 has selective activity against Aurora A and Flt3 with IC50 of 14 nM and 1.86 nM, 25-fold selective for Aurora A than over Aurora B and less potent to RET, SRC, NTRK1/TRKA, CSF1R/FMS, VEGFR2/KDR, FGFR and PDGFRα. ENMD-2076 inhibits the growth of a wide range of human solid tumor and hematopoietic cancer cell lines with IC50 from 0.025 to 0.7 μM, which induces apoptosis and G2/M phase arrest. Phase 2. |
Breast cancer cells line MDA-MB-231 were treated with the indicated concentrations of ENMD-2076.
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| S1220 |
OSI-930OSI-930 is a potent inhibitor of Kit (c-Kit), KDR and CSF-1R with IC50 of 80 nM, 9 nM and 15 nM, respectively; also potent to Flt-1, c-Raf and Lck and low activity against PDGFRα/β, Flt-3 and Abl. Phase 1. |
RE-luc2P-HEK293 cells were pretreated with 1uM OSI-930 (green), 20uM TBB (blue), 10uM CKI-7 (purple), or 10uM H-89 (orange) for 16 h and infected with Y. enterocolitica WA or Y. pestis Ind195 at MOI 1 and 20, respectively, for 1 h. Following stimulation with 10 ng/ml TNF-α at 5 h post-infection, luciferase activity was measured 24 h post-infection. Results were determined from two independent experiments performed in triplicate. A"*" denotes that the % NF-κβ inhibition using the inhibitors was significantly different (p<0.05) compared to the no drug control (black). The relative NF-κB inhibition by Yersinia infection was determined as a percentage of luciferase activity in bacteria-infected cells relative to luciferase activity in bacteria-free control cells.
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| S1171 |
CYC116CYC116 is a potent inhibitor of Aurora A/B with Ki of 8.0 nM/9.2 nM, is less potent to VEGFR2 (Ki of 44 nM), with 50-fold greater potency than CDKs, not active against PKA, Akt/PKB, PKC, no effect on GSK-3α/β, CK2, Plk1 and SAPK2A. Phase 1. |
Breast cancer cells line MDA-MB-231 were treated with the indicated concentrations of CYC116.
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| S1363 |
Ki8751Ki8751 is a potent and selective inhibitor of VEGFR2 with IC50 of 0.9 nM, >40-fold selective for VEGFR2 than c-Kit, PDGFRα and FGFR-2, little activity to EGFR, HGFR and InsR. |
Effect of select kinase inhibitors on DF508-CFTR maturation analyzed by immunoblotting. 293MSR-GT cells stably expressing DF508-CFTR were treated with 15 uM kinase inhibitors or 0.3% DMSO (vehicle control), as indicated, grown at 37 °C for 48 h, and the appearance of the mature protein, band C, monitored
by immunoblotting with anti-CFTR antibodies. Band B represents the immature protein. DMSO represents vehicle-alone control, 27 °C represents temperature rescue of F508-CFTR at 27 °C, 37 °C represents untreated DF508-CFTR control, and WT represents WT-CFTR. Top panels depict the anti-CFTR immunoblot and bottom panels depict actin (loading) control. ** represents cellular toxicity.
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| S2231 |
TelatinibTelatinib (BAY 57-9352) is a potent inhibitor of VEGFR2/3, c-Kit and PDGFRα with IC50 of 6 nM/4 nM, 1 nM and 15 nM, respectively. Phase 2. |
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| S2622 |
PP121PP-121 is a multi-targeted inhibitor of PDGFR, Hck, mTOR, VEGFR2, Src and Abl with IC50 of 2 nM, 8 nM, 10 nM, 12 nM, 14 nM and 18 nM, also inhibits DNA-PK with IC50 of 60 nM. |
PP121 induces apoptosis in ATC cells. CAL62 cells were treated with PP121 at the indicated concentrations for 48 h, followed by PI staining. The nuclei were stained with Hoechst and analyzed using a fluorescent microscope. The representative images are shown.
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| S3012 |
PazopanibPazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms/CSF1R with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. Pazopanib induces cathepsin B activation and autophagy. |
Three RCC cell lines treated with different concentrations of TKI and HDIL-2 and incubated for 48 h. Microscopic images show apoptotic materials 48 h following treatment (arrows show the apoptotic materials in the pazopanib-treated cells).
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| S1557 |
KRN 633KRN 633 is an ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 170 nM/160 nM/125 nM, weakly inhibits PDGFR-α/β and c-Kit, does not block the phosphorylation of FGFR-1, EGFR or c-Met in cell. |
Inhibited migration of hNSCs toward HeLa cells with the treatment of KRN633, a VEGFR2 inhibitor. The cultured hNSCs were treated with KRN633 for 6 h. After that, the transwell migration assay was performed as described above. The number of migrated cells was counted and the results were presented as means ± SD. Magnification,× 200. *P < 0.05 vs. KRN633 non-treated
GESTECs. (A) Migrated HB1.F3.CD cells. (B) Migrated HB1.F3.CD.IFN-β cells.
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| S2842 |
SAR131675SAR131675 is a VEGFR3 inhibitor with IC50/Ki of 23 nM/12 nM in cell-free assays, about 50- and 10-fold more selective for VEGFR3 than VEGFR1/2, little activity against Akt1, CDKs, PLK1, EGFR, IGF-1R, c-Met, Flt2 etc. |
Blockade of IPC-induced ischemic tolerance by the VEGFR-3 inhibitor SAR131675. (A) Representative images of FJ-stained brain sections from sham + SARH (i), sham-IPC + SI + Veh (ii), IPC + SI + Veh (iii) and IPC + SI + SARH (iv) groups. Note that there were more degenerated neurons in the IPC + SI + SARH group receiving SAR131675 of 50 mg/kg as an initial dose than in the IPC + SI + Veh group. Scale bar = 50 μm. (B) The quantitative analysis shows the number of FJ-positive degenerated neurons in the CA1 subregion of the different treatment groups including the IPC + SI + SARL group receiving SAR131675 of 25 mg/kg as an initial dose. Data are presented as the mean ± SEM; # p < 0.05 compared with the sham-IPC + SI + Veh group; *p < 0.05 compared with the IPC + SI + Veh group. (C) Representative images of NeuN immunofluorescence in the sham + SARH (i), sham-IPC + SI + Veh (ii), IPC + SI + Veh (iii) and IPC + SI + SARH (iv) groups. Note that NeuN-immunofluorescence in the IPC + SI + SARH group was reduced compared with the IPC + SI + Veh group. Scale bar = 50 μm. (D) The quantitative analysis shows the number of NeuN-positive intact pyramidal neurons in the CA1 subregion for the different treatment groups. Data are presented as the mean ± SEM; #p < 0.05 compared with the sham-IPC + SI + Veh group; *p < 0.05 compared with the IPC + SI + Veh group. |
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| S2201 |
BMS-794833BMS-794833 is a potent ATP competitive inhibitor of Met (c-Met)/VEGFR2 with IC50 of 1.7 nM/15 nM, also inhibits Ron, Axl and Flt3 with IC50 of <3 nM; a prodrug of BMS-817378. Phase 1. |
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| S7397 |
Sorafenib (BAY 43-9006)Sorafenib (BAY 43-9006, NSC-724772) is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity. |
Involvement of EV linc-VLDLR in tumor cell responses to chemotherapy. Cells were incubated with sorafenib, camptothecin, or doxorubicin. EVs were obtained after 24 hours, and qRT-PCR was performed for linc-VLDLR. The bars represent the mean ?SEM of the increase in cell viability from 3 independent studies. *, P < 0.05.
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| S4001 |
Cabozantinib malate (XL184)Cabozantinib malate (XL184) is the malate of Cabozantinib, a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret (c-Ret), Kit (c-Kit), Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. Cabozantinib malate (XL184) induces apoptosis. |
Effects of AXL inhibitors on induction of pAKT and rescue of pERK following AXL overexpression. R428, 500 nmol/L; XL184, 3 umol/L; XL880, 100 nmol/L; in the presence or absence of 2 umol/L PLX4720. shAXL is a positive control.
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| S1138 |
Brivanib Alaninate (BMS-582664)Brivanib alaninate (BMS-582664) is the prodrug of BMS-540215, an ATP-competitive inhibitor against VEGFR2 with IC50 of 25 nM. |
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| S2859 |
Golvatinib (E7050)Golvatinib (E7050) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, does not inhibit bFGF-stimulated HUVEC growth (up to 1000 nM). Phase 1/2. |
PC-9/LMC-GR cells (2 × 105 cells/well) were incubated in 6-well plates with various concentrations of gefitinib with or without crizotinib (1 μmol/L) or golvatinib (1 μmol/L) for 1 hour. Cell lysate were obtained and subjected to immunoblotting with antibodies toward the indicated molecules.
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| S2845 |
Semaxanib (SU5416)Semaxanib (SU5416) is a potent and selective VEGFR(Flk-1/KDR) inhibitor with IC50 of 1.23 μM, 20-fold more selective for VEGFR than PDGFRβ, lack of activity against EGFR, InsR and FGFR. Phase 3. |
Injected tumor cells move to the tail via blood vessels. Tg (flil1:egfp) embryos at 20 hpf were treated with 2 μM SU5416 for 1 hr (+SU5416) to inhibit vasculogenesis24; the control fish were treated with 0.02% DMSO for 1 hr (-SU5416). After 1 hr, SU5416 or DMSO was washed out by changing fish media. At 48 hpf, tfRFP-B16 cells were injected into the pericardium cavity of fish. Representative images show that tumor cells moved to the tail in a drug-free larva, while no tumor cells moved to the tail in a drug-treated larva after new vessels were inhibited by SU5416. Insets are enlarged images from each corresponding tip of the tail indicated by white arrows. Dashed white lines mark extravasated tumor cells at 12 hpi. Vessels are green and tumor cells are red. –SU5416, 6 other larvae exhibit similar behaviors; +SU5416, 3 other larvae exhibit similar behaviors. Scale bars, 500 μm. Insets, 100 μm.
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| S2897 |
ZM 306416ZM 306416 (CB 676475) is a VEGFR (Flt and KDR) inhibitor for VEGFR1 with IC50 of 0.33 μM, but also found to inhibit EGFR with IC50 of <10 nM. |
Panels D-F show morphological changes of RBEC cells due to Sema3A treatment. RBECs were fixed after the indicated treatment and stained with phalloidin conjugated with rhodamine (red color) and counter stained with DAPI (blue color). F-actin stress fibres are very clear in untreated cells (D). Sema3A treatment caused disruption of F-actin inside the cells. Densely packed bundles of cortical actin filaments started to appear along cell membranes (arrows) over the course of treatment with Sema3A. Antibodies and inhibitors against receptors of Sema3A were pre-incubated with the cells for 15 min before the addition of Sema3A. Antibodies to VEGFR1 and NRP2 (panel E) and the inhibitor Zm 306416 (selective to VEGFR1, panel F) were effective in ameliorating the effect of Sema3A. Scale bar=20 μm. |
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| S2896 |
ZM 323881 HClZM 323881 is a potent and selective VEGFR2 inhibitor with IC50 of <2 nM, almost no activity on VEGFR1, PDGFRβ, FGFR1, EGFR and ErbB2. |
(A) Fluorescence microscopic analysis of Hoechst 33342 staining of NCIH460 and NCI-H460/MX20 cells. Cells were treated as described in ‘2. Materials and Methods’. Scale bar, 10 μm. (B) Effects of ZM323881 on intracellular accumulation of [3H]-mitoxantrone in NCI-H460 and NCI-H460/MX20 cells. (C) Efflux of [3H]-mitoxantrone in the absence and presence of inhibitors in NCI-H460 cells. (D) Efflux of [3H]-mitoxantrone in the absence and presence of inhibitors in NCI-H460/MX20 cells.
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| S2018 |
ENMD-2076 L-(+)-Tartaric acidENMD-2076 L-(+)-Tartaric acid is the tartaric acid of ENMD-2076, selective activity against Aurora A and Flt3 with IC50 of 14 nM and 1.86 nM, 25-fold more selective for Aurora A than Aurora B and less potent to VEGFR2/KDR and VEGFR3, FGFR1 and FGFR2 and PDGFRα. Phase 2. |
Breast cancer cells line MDA-MB-231 were treated with the indicated concentrations of ENMD-2076.
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| S7057 |
LY2874455LY2874455 is a pan-FGFR inhibitor with IC50 of 2.8 nM, 2.6 nM, 6.4 nM, and 6 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively, and also inhibits VEGFR2 activity with IC50 of 7 nM. Phase 1. |
A: Overall structure of LY2874455/FGFR4 complex. B: The diagram of LY2874455. C: Fo-Fc omit map of LY2874455 in the FGFR4/LY2874455 complex. The electron density is superimposed with the final model. D: The DFG motif conformation of FGFR4. Active ApoFGFR4 DFG-in conformation is shown in blue (PDB: 4QQT); FGFR4/Ponatinib DFG-out conformation is shown in yellow (PDB: 4UXQ); FGFR4/BLU9931 DFG-in conformation is shown in pink (PDB: 4XCU); FGFR4/LY2874455 DFG-in conformation is shown in grey (this work). LY2874455 is highlighted in brown.
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| S8189 |
BAW2881 (NVP-BAW2881)BAW2881 (NVP-BAW2881) is a novel vascular endothelial growth factor (VEGF) receptor tyrosine-kinase inhibitor that potently inhibits VEGFR1-3 at 1.0-4.3 nanomolar (nM) concentrations and inhibits PDGFRβ, c-Kit, and RET (c-RET) at 45-72 nM concentrations. |
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| S6520 |
WHI-P180WHI-P180 is a multi-kinase inhibitor with IC50 values of 4.5 and 66 nM for the human proto-oncogene RET (c-RET) and kinase insert domain receptor (KDR), respectively. |
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| S0504 |
SU14813SU14813 (SU 014813) is a multiple receptor tyrosine kinase inhibitor with IC50 of 50 nM, 2 nM, 4 nM and 15 nM for VEGFR2, VEGFR1, PDGFRβ and Kit (c-Kit). SU14813 exhibits potent antiangiogenic and antitumor activity. |
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| S6543 |
ZD-4190ZD-4190 is a submicromolar inhibitor of VEGF RTK activity in vitro with IC50 values of 29 ± 4 nM and 708 ± 63 nM for KDR and Flt-1, respectively. |
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| S6535 |
SU1498SU1498, a powerful inhibitor of KDR (IC50 = 0.7 μM), stimulates accumulation of phosphorylated ERK1/2 in endothelial cells. |
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| S7667 |
SU5402SU5402 is a potent multi-targeted receptor tyrosine kinase inhibitor with IC50 of 20 nM, 30 nM, and 510 nM for VEGFR2, FGFR1, and PDGF-Rβ, respectively. |
Four FGFR inhibitors, namely PD-173074 (PD-74), PD-166866 (PD-66), SU5402 (SU54) and NVP-BGJ398 (BG-98), inhibit A673, SKNMC, POE, RDES and SKES Ewing cell growth in vitro in a dose-dependent manner, whereas normal cells (IMR90 fibroblasts) remained unaffected. PD-74 proved to be most effective in four out of five Ewing sarcoma cell lines tested. Cells were grown in 10% FBS conditions and cell proliferation was measured after 72 h using a Resazurin assay.
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| S8721 |
PDGFR inhibitor 1PDGFR inhibitor 1 is an orally bioavailable switch pocket control inhibitor of wild-type and mutated forms of Kit (c-Kit) and PDGFR with potential antineoplastic activity. It also inhibits several other kinases, including VEGFR2, TIE2, PDGFR-beta and CSF1R, thereby further inhibiting tumor cell growth. |
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| S7688 |
Ki20227Ki20227 is an orally active and highly selective inhibitor of c-Fms tyrosine kinase(CSF1R) with IC50 of 2 nM, 12 nM, 451 nM and 217 nM for c-Fms, vascular endothelial growth factor receptor-2 (KDR/VEGFR-2), stem cell factor receptor (c-Kit), and platelet-derived growth factor receptor beta (PDGFRβ), respectively. |
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| S7765 |
Dovitinib (TKI258) LactateDovitinib (TKI258, CHIR258) Lactate is the Lactate of Dovitinib, which is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGFR1 and HER2. Phase 4. |
(c) Percent survival for the AGS cancer cell line is shown with FGFR2 inhibitors of varying specificity. (d) The KatoIII diffuse gastric cancer cell line was treated with FGFR2 inhibitors of varying specificity. The Y-axis depicts percent survival versus the X-axis with log concentrations. In all panels, error bars represent standard error of the mean. The difference in percent cell survival between KatoIII and AGS cells was statistically significant (P <0.05) at the three highest concentrations of all drugs, except Brivanib which was only significant at the highest concentration. |
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| S5272 |
Toceranib phosphateToceranib phosphate (Palladia, SU11654), the phosphate salt of toceranib, is a selective inhibitor of the tyrosine kinase activity of several members of the split kinase RTK family, including Flk-1/KDR, PDGFR, and Kit with Ki values of 6 nM and 5 nM for Flk-1/KDR and PDGFRβ, respectively. |
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| S5242 |
Cediranib MaleateCediranib Maleate (AZD-2171) is the maleate salt of Cediranib, which is a potent inhibitor of VEGFR with IC50 of <1 nM and also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM. |
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| S8188 |
BFH772BFH772 is a novel potent oral VEGFR2 inhibitor, targeting VEGFR2 kinase with IC50 of 3 nM. |
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| S5240 |
Lenvatinib (E7080) MesylateLenvatinib Mesylate (E7080) is a synthetic, orally available tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR1-3), fibroblast growth factor receptor (FGFR1-4), platelet-derived growth factor receptor α (PDGFRα), stem cell factor receptor (Kit (c-Kit)), and rearranged during transfection (RET (c-RET)). Lenvatinib Mesylate has potential antineoplastic activity. |
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| S0278 |
SU5614SU5614 (Chloro-SU5416, Chloro-Semaxanib) is a small molecule receptor tyrosine kinases (RTK) inhibitor of VEGFR-2, c-kit, and both wild-type and mutant FLT3. SU5614 reduces cell proliferation and induces apoptosis. |
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| S0290 |
SU5204SU5204, an analogue of SU5025, is a pharmacological inhibitor of VEGFR2. |
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| S5667 |
Fruquintinib (HMPL-013)Fruquintinib (HMPL-013) is a small molecule inhibitor with strong potency and high selectivity against VEGFR family. It inhibits VEGFR 1, 2, 3, with IC50 values of 33 nM, 35 nM and 0.5 nM, respectively and shows only weak inhibition of RET, FGFR-1 and c-kit kinases. |
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| S8882 |
ODM-203ODM-203 is a selective inhibitor of FGFR and VEGFR with ic50s of 11 nM,16 nM,6 nM, 35 nM,26 nM,9 nM,5 nM for recombinant FGFR1, FGFR2, FGFR3,FGFR4, VEGFR1, VEGFR2 and VEGFR3, respectively. |
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| S8401 |
Erdafitinib (JNJ-42756493)Erdafitinib (JNJ-42756493) is a potent and selective orally bioavailable, pan fibroblast growth factor receptor (FGFR) inhibitor with potential antineoplastic activity. Erdafitinib also binds to RET (c-RET), CSF-1R, PDGFR-α/PDGFR-β, FLT4, Kit (c-Kit) and VEGFR-2 and induces cellular apoptosis. |
E, Continuous ERK phosphorylation in FGFR inhibitor resistant cells under 24-hour treatment with 1 μmol/L BGJ398 assessed by immunoblotting. FGFR inhibitors: AZD4547, BGJ398, and JNJ-42756493 |
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| S0765 |
MAZ51MAZ51 is a potent and selective inhibitor of vascular endothelial growth factor receptor (VEGFR)-3 (Flt-4) tyrosine kinase. MAZ51 induces cell rounding and G2/M cell cycle arrest in glioma cells through phosphorylation of Akt/GSK3β and activation of RhoA. MAZ51 inhibits the proliferation and induces the apoptosis of a variety of non-VEGFR-3-expressing tumor cell lines. |
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| S6526 |
SKLB 610SKLB-610 is a multi-target inhibitor of the tyrosine kinases. It is most potent against VEGFR2 and exhibits slightly weaker inhibitor of FGFR2 and PDGFR. |
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| S7781 |
Sunitinib (SU11248)Sunitinib (SU11248) is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit. Sunitinib is also a dose-dependent inhibitor of the autophosphorylation activity of IRE1α. Sunitinib induces autophagy and apoptosis. |
Sunitinib decreases FLT-3 and RET phosphor ylation but increases ERK phosphorylation in a time-dependent manner. H295R and SW13 cells were treated with sunitinib (10 nM) for various time points as indi-cated. Cell lysates were prepared and phospho-FLT-3, RET, and ERK levels were monitored by Western Blot-ting. Re-probing against FLT-3, RET, and ERK was done to ensure equal protein loading. |
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| S8573 |
Sitravatinib (MGCD516)Sitravatinib (MGCD516, MG-516) is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth, including c-Kit, PDGFRβ, PDGFRα, c-Met, and Axl. |
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| S9621 |
Donafenib (Sorafenib D3)Donafenib (Sorafenib D3, Bay 43-9006 D3, CM-4307) is the deuterium labeled Sorafenib. Sorafenib is a multikinase inhibitor IC50s of 6 nM, 15 nM, 20 nM and 22 nM for Raf-1, mVEGFR-2, mVEGFR-3 and B-RAF, respectively. |
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| S2211 |
AG-13958AG-13958 (AG-013958), a VEGFR tyrosine kinase inhibitor, is in clinical development with ST administration for treatment of choroidal neovascularization associated with age–related macular degeneration (AMD). |
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| S7258 |
SKLB1002SKLB1002 is a potent and ATP-competitive VEGFR2 inhibitor with IC50 of 32 nM. |
Protein expressions of VEGFR2, p-VEGFR2, FAK, p-FAK, ERK, p-ERK and VE-cadherin in HCT116 cells with or without SKLB1002 treatment were determined by western blotting analysis. Representative data of three experiments are shown
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| S5793 |
Motesanib (AMG-706)Motesanib (AMG-706) is an orally bioavailable receptor tyrosine kinase inhibitor with IC50 values of 2 nM, 3 nM, 6 nM, 8 nM, 84 nM, 59 nM for VEGFR1, VEGFR2, VEGFR3, Kit, PDGFR and Ret, respectively. |
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| S6870 |
NingetinibNingetinib (CT-053, DE-120, CT053PTSA) is a potent, orally bioavailable inhibitor of tyrosine kinase with IC50 of 6.7 nM, 1.9 nM and <1.0 nM for c-Met, VEGFR2 and Axl, respectively. Ningetinib exhibits antitumor activity. |
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| S6843 |
X-82 (Vorolanib)X-82 (Vorolanib, CM082) is an oral, multikinase, dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) with antiangiogenic and antineoplastic activities. |
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| S0377 |
CS-2660 (JNJ-38158471)CS-2660 (JNJ-38158471) 是一种耐受性良好的、口服有效的、高选择性的 VEGFR-2 抑制剂，IC50值为40 nM。CS-2660（JNJ-38158471）还抑制紧密相关的酪氨酸激酶，如 RET (c-RET) 和 Kit (c-Kit)，IC50为180 nM和500 nM，但无明显活性 (>1 microM) 针对VEGFR-1和VEGFR-3。 |
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| S8696 |
2-D082-D08 (2',3',4'-trihydroxy flavone) is a cell permeable, mechanistically unique inhibitor of protein sumoylation. It is also inhibits Axl, IRAK4, ROS1, MLK4, GSK3β, RET (c-RET), KDR and PI3Kα with IC50 values of 0.49, 3.9, 5.3, 9.8, 11, 11, 17 and 35 nM respectively in biochemical assays. |
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| S6412 |
AltiratinibAltiratinib (DCC-2701) is a potent single-digit nanomolar inhibitor of TRK, Met (c-Met), TIE2, and VEGFR2 kinases with IC50 vaules of 0.9 nM, 4.6 nM, and 0.8 nM for TRKA, B, and C, respectively. It inhibits Met (c-Met) and Met (c-Met) mutant with IC50 values in the range of 0.3-6 nM. |
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| S4686 |
Vitamin EVitamin E (D-alpha-Tocopherol) is a fat-soluble vitamin with potent antioxidant properties. It is a potent peroxyl radical scavenger and inhibits noncompetitively cyclooxygenase activity in many tissues, also inhibits angiogenesis and tumor dormancy through suppressing vascular endothelial growth factor (VEGF) gene transcription. |
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| S6514 |
SU5408SU5408 (VEGFR2 Kinase Inhibitor I) is a potent and selective inhibitor of VEGFR2 Kinase with IC50 of 70 nM. |
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| S7003 |
AZD2932AZD2932 is a potent and mutil-targeted protein tyrosine kinase inhibitor with IC50 of 8 nM, 4 nM, 7 nM, and 9 nM for VEGFR-2, PDGFRβ, Flt-3, and c-Kit, respectively. |
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| S8726 |
Anlotinib (AL3818) dihydrochlorideAnlotinib (AL3818) is a highly potent and selective VEGFR2 inhibitor with IC50 less than 1 nM. It has broad-spectrum antitumor potential in clinical trials. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation. |
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