オーロラ・キナーゼ
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 | ||
| S1133 | Alisertib (MLN8237) | <1 mg/mL | 27 mg/mL | '<1 mg/mL |
| S1048 | Tozasertib | <1 mg/mL | 93 mg/mL | '''<1 mg/mL |
| S1460 | SP600125 | <1 mg/mL | 44 mg/mL | <1 mg/mL |
| S1147 | Barasertib (AZD1152-HQPA) | <1 mg/mL | 102 mg/mL | '3 mg/mL |
| S1103 | ZM 447439 | <1 mg/mL | 103 mg/mL | <1 mg/mL |
| S1100 | MLN8054 | <1 mg/mL | 95 mg/mL | <1 mg/mL |
| S1107 | Danusertib (PHA-739358) | <1 mg/mL | 95 mg/mL | <1 mg/mL |
| S1134 | AT9283 | <1 mg/mL | 76 mg/mL | 38 mg/mL |
| S1249 | JNJ-7706621 | <1 mg/mL | 79 mg/mL | <1 mg/mL |
| S1529 | Hesperadin | <1 mg/mL | 103 mg/mL | <1 mg/mL |
| S1451 | Aurora A Inhibitor I (TC-S 7010) | <1 mg/mL | 118 mg/mL | <1 mg/mL |
| S2158 | KW-2449 | <1 mg/mL | 67 mg/mL | 67 mg/mL |
| S1154 | SNS-314 | 6 mg/mL | 105 mg/mL | <1 mg/mL |
| S1181 | ENMD-2076 | 1 mg/mL | 105 mg/mL | <1 mg/mL |
| S1454 | PHA-680632 | <1 mg/mL | 100 mg/mL | <1 mg/mL |
| S2770 | MK-5108 (VX-689) | <1 mg/mL | 92 mg/mL | <1 mg/mL |
| S1171 | CYC116 | <1 mg/mL | 24 mg/mL | <1 mg/mL |
| S2719 | AMG-900 | <1 mg/mL | 100 mg/mL | <1 mg/mL |
| S1519 | CCT129202 | <1 mg/mL | 3 mg/mL | <1 mg/mL |
| S2740 | GSK1070916 | <1 mg/mL | 93 mg/mL | '8 mg/mL |
| S2718 | TAK-901 | <1 mg/mL | 101 mg/mL | <1 mg/mL |
| S2744 | CCT137690 | <1 mg/mL | 4 mg/mL | <1 mg/mL |
| S7065 | MK-8745 | <1 mg/mL | 86 mg/mL | 1 mg/mL |
| S2018 | ENMD-2076 L-(+)-Tartaric acid | <1 mg/mL | 100 mg/mL | <1 mg/mL |
| S8699 | SNS-314 Mesylate | <1 mg/mL | 86 mg/mL | 1 mg/mL |
| S8782 | LY3295668 | <1 mg/mL | 98 mg/mL | ''''15 mg/mL |
| S2931 | Aurora Kinase Inhibitor III | <1 mg/mL | 83 mg/mL | 5 mg/mL |
| S7588 | Reversine | <1 mg/mL | 5 mg/mL | <1 mg/mL |
| S9658 | SP-96 | <1 mg/mL | 91 mg/mL | 2 mg/mL |
| S6214 | H-1152 dihydrochloride | 78 mg/mL | 78 mg/mL | ''78 mg/mL |
| S7843 | BI-847325 | <1 mg/mL | 19 mg/mL | 1 mg/mL |
| S1272 | XL228 | <1 mg/mL | 88 mg/mL | 30 mg/mL |
亜型選択性的な製品
Aurora Kinase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 |
|---|---|---|---|
| S1133 |
Alisertib (MLN8237)Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3. |
-S113303W0120130926.gif)
-S113303W0120130926.gif)
Alisertib inhibits AURKA and AURKB in a concentration-dependent manner. (a) Alisertib induces G 2 /M delay or genome reduplication. HeLa cells were exposed to buffer or the indicated concentrations of Alisertib. After 24 h, the cells were harvested and analyzed with flow cytometry. The positions of 2N, 4N and 8N DNA contents are indicated. (b) Alisertib delays mitotic exit or induces slippage. HeLa cells stably expressing histone H2B-GFP were exposed to buffer or the indicated concentrations of Alisertib. Individual cells were then tracked for 24 h with time-lapse microscopy. Each horizontal bar represents one cell (n ¼ 50). Key: light gray ¼ interphase; black ¼ mitosis (from DNA condensation to anaphase or mitotic slippage); dark gray ¼ interphase after mitotic slippage; truncated bars ¼ cell death. (c) Different concentrations of Alisertib are involved in delaying mitotic exit and inducing slippage. Live-cell imaging of cells treated with Alisertib was described in panel (b). The duration of mitosis (mean±90% confidence interval) and the percentage of cells that underwent mitotic slippage during the imaging period was quantified. (d) Alisertib promotes apoptosis in a concentration-dependent manner. HeLa cells were incubated with the indicated concentrations of Alisertib for 48 h. The cells were then harvested and analyzed with flow cytometry. (e) Concentration-dependent cytotoxicity of Alisertib. HeLa cells were cultured in the presence of the indicated concentrations of Alisertib for 48 h. The number of live and dead cells was analyzed with trypan blue exclusion assay. (f) Concentration-dependent suppression of long-term survival by Alisertib. HeLa cells were seeded on 60-mm culture plates and grown in the presence of 250 n M or 1 m M of Alisertib. After 24 h, the cells were washed gently and propagated in normal medium for another 10–12 days. Colonies were fixed and stained with crystal violet solution (examples of the plates are shown). Average±s.d. from three independent experiments. (g) Both AURKA and AURKB are inhibited by Alisertib.Mitotic HeLa cells were obtained by exposure to nocodazole for 16 h followed by mechanical shake off. The cells were incubated with the indicated concentrations of Alisertib for 2 h. Lysates were then prepared and activated phospho-AURKAThr288 and AURKBThr232were detected with immunoblotting. The asterisk indicates the position of an AURKB-like protein (the same throughout this study). Uniform loading was confirmed by immunoblotting for actin. In this assay, nocodazole and MG132 (a proteasome inhibitor) were added to prevent the cells from exiting mitosis. Accordingly, the total AURKA and AURKB levels remained constant throughout the experiment. (h) Alisertib prevents activation of AURKA and AURKB. HeLa cells were incubated with the indicated concentrations of Alisertib for 8 h. Nocodazole was then added for another 6 h to trap cells that entered mitosis. Lysates were prepared and analyzed with immunoblotting. Actin analysis was included to assess loading and transfer. |
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| S1048 |
TozasertibTozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with Kiapp of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. The only exceptions are Fms-related tyrosine kinase-3 (FLT-3) and BCR-ABL tyrosine kinase, which are inhibited by the Tozasertib with both Ki of 30 nM. Tozasertib induces apoptosis and autophagy. Phase 2. |
Senescence induction upon PKCι depletion combined with aurora kinase inhibition. ( a) MCF7 cells were transfected as above to deplete PKCι . Two days after transfection, cells were treated for the indicated time period with 400 n M VX-680. Medium with VX-680 was then removed and fresh medium was added. Cells were stained for SA-b -gal activity 5 days after the start of transfection.* indicates a P value <0.05. ( b) MCF7 cells were treated as above. Five days after transfection, cells were fixed and assessed for the presence of gH2AX foci by immunofluorescence microscopy. (c, d) MCF7 cells were treated with dimethyl sulfoxide (DMSO) control or 400 n M VX-680 for the indicated time periods. Total cell lysates were then analyzed by western blotting for levels of p21 and GAPDH (as loading control). A representative blot is shown in panel c. Quantitation of changes in p21 levels (normalized to vehicle-treated controls) is shown in panel d. The data shown are the means ±s.e. of three independent experiments. |
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| S1460 |
SP600125SP600125 (Nsc75890) is a broad-spectrum JNK inhibitor for JNK1, JNK2 and JNK3 with IC50 of 40 nM, 40 nM and 90 nM in cell-free assays, respectively; 10-fold greater selectivity against MKK4, 25-fold greater selectivity against MKK3, MKK6, PKB, and PKCα, and 100-fold selectivity against ERK2, p38, Chk1, EGFR etc. SP600125 is also a broad‐spectrum inhibitor of serine/threonine kinases including Aurora kinase A，FLT3 and TRKA with of IC50 of 60 nM, 90 nM and 70 nM. SP600125 inhibits autophagy and activates apoptosis. |
Loss of DUSP4 function upregulates IL-6 and IL-8 and enhances mammosphere growth. Immunoblot analysis of MDA-231 cells after treatment of 24 hours with 1 umol/L selumetinib (MEKi) or 10 umol/L SP600125 (JNKi). I, MDA-231 mammosphere formation quantitated by GelCount software 7 days after siRNA transfection. Where indicated, selumetinib (MEKi) or SP600125 (JNK1) or the combination was added to the mammosphere cultures.
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| S1147 |
Barasertib (AZD1152-HQPA)Defosbarasertib (AZD1152-HQPA, AZD2811, INH-34, Barasertib-HQPA) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, ~3700 fold more selective for Aurora B over Aurora A. Phase 1. |
Targeting PI3K, a common downstream effector of RTKs, with a selective inhibitor (GDC0941) sensitizes SOX10 knockdown cells to vemurafenib. shRNAs targeting SOX10 were introduced into A375 cells by lentiviral transduction. pLKO.1 empty vector served as a control vector (Ctrl). Cells were seeded in 6-well plates at the same density in the presence or absence of drug(s) at the indicated concentration. Cells were cultured for 2 weeks in the absence of vemurafenib or 4 weeks in the presence of vemurafenib before fixing and staining.
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| S1103 |
ZM 447439ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc. |
p31comet depletion delays MCC disassembly even with the proteasome inhibited. (A) FACS analysis of HeLa Tet-on cells transfected with control or p31comet siRNA and then treated with Taxol followed by Aurora B inhibition with ZM447439. The percentage of mitotic cells (cells that have 4N DNA content and are MPM2 positive) is shown for each sample. |
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| S1100 |
MLN8054MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM in Sf9 insect cell. It is more than 40-fold selective for Aurora A than Aurora B. Phase 1. |
Stacked column graphic representing the effect of the small molecule MLN8054 throughout oocyte developmental progress, namely during metaphase I, telophase I and metaphase II oocytes in different conditions. |
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| S1107 |
Danusertib (PHA-739358)Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib induces apoptosis, cell cycle arrest, and autophagy. Phase 2. |
Mice bearing subcutaneous allografts of conditional patched mutant tumor cells were treated twice weekly with vehicle (saline) or 30 mg/kg PHA-739358. (B)Images of tumors. (C) Tumor weights. Each point represents a single tumor, and grey lines represent mean tumor weights, which were significantly different between vehicle and PHA-739358 treated mice (p < 0.05, based on paired two-tailed t-test).
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| S1134 |
AT9283AT9283 is a potent JAK2/3 inhibitor with IC50 of 1.2 nM/1.1 nM in cell-free assays; also potent to Aurora A/B, Abl1(T315I). Phase 2. |
HEL cells were treated with 0.5, 1 or 5 uM of AT9283 or left untreated for 3 hrs. The expression and phosphorylation state of STAT5 (P-STAT5) and Jak2 (P-Jak2) was assessed by Western blot immunodetection.
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| S1249 |
JNJ-7706621JNJ-7706621 is pan-CDK inhibitor with the highest potency on CDK1/2 with IC50 of 9 nM/4 nM and showing >6-fold selectivity for CDK1/2 than CDK3/4/6 in cell-free assays. It also potently inhibits Aurora A/B and has no activity on Plk1 and Wee1. |
JNJ-7706621 treatment of tamoxifen-resistant cell lines leads to arrest in the G2 cell cycle phase. M phase cells from the upper right quadrants were quantified relative to total G2/M phase cells. Statistical significant differences from vehicle-treated cells are denoted by asterisks; *P<0.05, **P<0.01.
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| S1529 |
HesperadinHesperadin potently inhibits Aurora B with IC50 of 250 nM in a cell-free assay. It markedly reduces the activity of AMPK, Lck, MKK1, MAPKAP-K1, CHK1 and PHK while it does not inhibit MKK1 activity in vivo. |
HeLa cells treated with nocodazole containing DMSO or Hesperadin (100 nM) for 2 h and stained with the indicated antibodies. |
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| S1451 |
Aurora A Inhibitor I (TC-S 7010)Aurora A Inhibitor I (TC-S 7010) is a novel, potent, and selective inhibitor of Aurora A with IC50 of 3.4 nM in a cell-free assay. It is 1000-fold more selective for Aurora A than Aurora B. Aurora A Inhibitor I (TC-S 7010) triggers apoptosis through the ROS-mediated UPR signaling pathway. |
Aurora-A inhibitors severely impair neuronal migration. Migration of granular neurons after treatment of Aurora-A inhibitors was examined. a, Western blotting analysis of proteins or phosphorylated proteins. Aurora-A and NDEL1 displayed similar expression levels, whereas phosphorylated Aurora-A and NDEL1 proteins were decreased during treatment with Aurora-A inhibitors. Relative intensities of the bands of Western blotting are displayed at the bottom. |
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| S2158 |
KW-2449KW-2449 is a multiple-targeted inhibitor, mostly for Flt3 with IC50 of 6.6 nM, modestly potent to FGFR1, Bcr-Abl and Aurora A; little effect on PDGFRβ, IGF-1R, EGFR. Phase 1. |
Western blot analysis of p-histone and histone. 0-10μM KW2449 was added.
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| S1154 |
SNS-314SNS-314 Mesylate is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively. It is less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2. Phase 1. |
Nuclear morphology and cell cycle distribution (green for phases G2/M, and red for phase G1) of NMuMG-Fucci cells exposed to 1 uM SNS-314 for 96 h.
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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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| S1454 |
PHA-680632PHA-680632 is potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, respectively. It has 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, and VEGFR2/3. |
Quantification of phT288-AURKA expression as in figure n=3, normalized to total AURKA and plotted as relative intensity units (RIU) +/- S.E.M. Two-way ANOVA, p<0.0001, (shCon/shN1 or shN2), p=0.0013 (shN1/shN2).
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| S2770 |
MK-5108 (VX-689)MK-5108 (VX-689) is a highly selective Aurora A inhibitor with IC50 of 0.064 nM in a cell-free assay and is 220- and 190-fold more selective for Aurora A than Aurora B/C, while it inhibits TrkA with less than 100-fold selectivity. MK-5108 (VX-689) induces autophagy. Phase 1. |
-S277001W0220130927.gif)
-S277001W0220130927.gif)
MK-5108 specifically inhibits AURKA and delays mitotic exit. (a) MK-5108 inhibits AURKA but not AURKB. Mitotic HeLa cells were obtained by exposure to nocodazole for 16 h followed by mechanical shake off. The cells were incubated with the indicated concentrations of MK-5108 for 2 h. Nocodazole and MG132 were included to prevent mitotic exit. Lysates were then prepared and activated phospho-AURKAThr288 and AURKBThr232 were detected with immunoblotting. Uniform loading was confirmed by immunoblotting for actin. (b) MK-5108 prevents activation of AURKA but not AURKB. HeLa cells were incubated with the indicated concentrations of MK-5108 for 8 h. Nocodazole was then added for another 6 h to trap any cells that entered mitosis. Mitotic cells were isolated by mechanical shake off. Lysates were prepared and analyzed with immunoblotting. Actin analysis was included to assess loading and transfer. (c) MK-5108 induces a G 2 /M delay. HeLa cells were treated with the indicated concentrations of MK-5108 for 24 h. DNA contents were analyzed with flow cytometry. |
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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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| S2719 |
AMG-900AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor for Aurora A/B/C with IC50 of 5 nM/4 nM /1 nM. It is >10-fold selective for Aurora kinases than p38α, Tyk2, JNK2, Met and Tie2. Phase 1. |
AURK inhibitors have significant cytotoxic effect on PCa cells. The cytotoxic effects of the AURK inhibitors were measured by MTS assay after 72 h treatment with these inhibitors. The viability fraction was compared to the untreated cells for each cell line. Error bars represent the SEM. C. Relative cell vability of PCa cells treated with AMG 900 at the concentrations of 0.05, 0.25 and 1.25 μmol/l. |
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| S1519 |
CCT129202CCT129202 is an ATP-competitive pan-Aurora inhibitor for Aurora A, Aurora B and Aurora C with IC50 of 0.042 μM, 0.198 μM and 0.227 μM, respectively. It is less potent to FGFR3, GSK3β, PDGFRβ, etc. |
T47D Breast cancer cells were pretreated with p-Aurora, Aurora and then treated with the indicated concentrations of CCT129202.
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| S2740 |
GSK1070916GSK1070916 is a reversible and ATP-competitive inhibitor of Aurora B/C with IC50 of 3.5 nM/6.5 nM. It displays >100-fold selectivity against the closely related Aurora A-TPX2 complex. Phase 1. |
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| S2718 |
TAK-901TAK-901 is a novel inhibitor of Aurora A/B with IC50 of 21 nM/15 nM. It is not a potent inhibitor of cellular JAK2, c-Src or Abl. Phase 1. |
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| S2744 |
CCT137690CCT137690 is a highly selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 15 nM, 25 nM and 19 nM. It has little effect on hERG ion-channel. |
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| S7065 |
MK-8745MK-8745 is a potent and selective Aurora A inhibitor with IC50 of 0.6 nM, more than 450-fold selectivity for Aurora A over Aurora B. |
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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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| S8699 |
SNS-314 MesylateSNS-314 Mesylate is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively and less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2. |
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| S8782 |
LY3295668LY3295668 (AK-01) is a potent, orally active and specific inhibitor of Aurora A kinase with Ki of 0.8 nM and 1038 nM for AURKA and AURKB, respectively. |
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| S2931 |
Aurora Kinase Inhibitor IIIAurora kinase inhibitor III is a potent inhibitor of Aurora A kinase with an IC50 of 42 nM and has high selectivity for Aurora A over BMX, BTK, IGF-1R, c-Src, TRKB, SYK, and EGFR (IC50s = 386, 3,550, 591, 1,980, 2,510, 887, and >10,000 nM, respectively). |
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| S7588 |
ReversineReversine is a potent human A3 adenosine receptor antagonist with Ki of 0.66 μM, and a pan-aurora A/B/C kinase inhibitor with IC50 of 12 nM/13 nM/20 nM, respectively. Also used for stem cell dedifferentiation. |
Immunofluorescence of acetylated a-tubulin (red) in control (a), reversin-treated (b), and BI 2536/Reversin mixture-treated embryos (c).The embryos treated with Reversine completed first mitosis, but the nuclei of their blastomeres were fragmented (b, arrows). Embryos inhibited withthe BI 2536/Reversine mixture arrested before the onset of anaphase. Microtubules of the spindle are disorganized (c, double-arrow) and thechromosomes are misaligned (c, arrows) in these inhibited embryos. DNA is counter-stained with DAPI (blue). Scale bar, 10 μm. |
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| S9658 |
SP-96SP-96 is a potent, selective and non-ATP-competitive inhibitor of Aurora B with IC50 of 0.316 nM. SP-96 can be used for the research of triple negative breast cancer (TNBC). |
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| S6214 |
H-1152 dihydrochlorideH-1152 dihydrochloride (2HCl) is a membrane-permeable and selective inhibitor of Rho-associated protein kinase (ROCK). H-1152 inhibits ROCK2, PKA, PKC, PKG, AuroraA and CaMK2 with IC50 of 0.0120 μM, 3.03 μM, 5.68 μM, 0.360 μM, 0.745 μM and 0.180 μM, respectively. |
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| S7843 |
BI-847325BI-847325 is an orally bioavailable, and selective dual MEK/Aurora kinase inhibitor with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM for Xenopus laevis Aurora B, human Aurora A and Aurora C, as well as human MEK1 and MEK2, respectively. Phase 1. |
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| S1272 |
XL228XL228 is a protein kinase inhibitor with IC50 of 5 nM, 1.4 nM, 3.1 nM, 1.6 nM, 6.1 nM and 2 nM for wild-type ABL kinase, ABL T315I, Aurora A, IGF-1R, SRC and LYN, respectively. |
| 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 |
|---|---|---|---|
| S1133 |
Alisertib (MLN8237)Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3. |
-S113303W0120130926.gif)
-S113303W0120130926.gif)
Alisertib inhibits AURKA and AURKB in a concentration-dependent manner. (a) Alisertib induces G 2 /M delay or genome reduplication. HeLa cells were exposed to buffer or the indicated concentrations of Alisertib. After 24 h, the cells were harvested and analyzed with flow cytometry. The positions of 2N, 4N and 8N DNA contents are indicated. (b) Alisertib delays mitotic exit or induces slippage. HeLa cells stably expressing histone H2B-GFP were exposed to buffer or the indicated concentrations of Alisertib. Individual cells were then tracked for 24 h with time-lapse microscopy. Each horizontal bar represents one cell (n ¼ 50). Key: light gray ¼ interphase; black ¼ mitosis (from DNA condensation to anaphase or mitotic slippage); dark gray ¼ interphase after mitotic slippage; truncated bars ¼ cell death. (c) Different concentrations of Alisertib are involved in delaying mitotic exit and inducing slippage. Live-cell imaging of cells treated with Alisertib was described in panel (b). The duration of mitosis (mean±90% confidence interval) and the percentage of cells that underwent mitotic slippage during the imaging period was quantified. (d) Alisertib promotes apoptosis in a concentration-dependent manner. HeLa cells were incubated with the indicated concentrations of Alisertib for 48 h. The cells were then harvested and analyzed with flow cytometry. (e) Concentration-dependent cytotoxicity of Alisertib. HeLa cells were cultured in the presence of the indicated concentrations of Alisertib for 48 h. The number of live and dead cells was analyzed with trypan blue exclusion assay. (f) Concentration-dependent suppression of long-term survival by Alisertib. HeLa cells were seeded on 60-mm culture plates and grown in the presence of 250 n M or 1 m M of Alisertib. After 24 h, the cells were washed gently and propagated in normal medium for another 10–12 days. Colonies were fixed and stained with crystal violet solution (examples of the plates are shown). Average±s.d. from three independent experiments. (g) Both AURKA and AURKB are inhibited by Alisertib.Mitotic HeLa cells were obtained by exposure to nocodazole for 16 h followed by mechanical shake off. The cells were incubated with the indicated concentrations of Alisertib for 2 h. Lysates were then prepared and activated phospho-AURKAThr288 and AURKBThr232were detected with immunoblotting. The asterisk indicates the position of an AURKB-like protein (the same throughout this study). Uniform loading was confirmed by immunoblotting for actin. In this assay, nocodazole and MG132 (a proteasome inhibitor) were added to prevent the cells from exiting mitosis. Accordingly, the total AURKA and AURKB levels remained constant throughout the experiment. (h) Alisertib prevents activation of AURKA and AURKB. HeLa cells were incubated with the indicated concentrations of Alisertib for 8 h. Nocodazole was then added for another 6 h to trap cells that entered mitosis. Lysates were prepared and analyzed with immunoblotting. Actin analysis was included to assess loading and transfer. |
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| S1048 |
TozasertibTozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with Kiapp of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. The only exceptions are Fms-related tyrosine kinase-3 (FLT-3) and BCR-ABL tyrosine kinase, which are inhibited by the Tozasertib with both Ki of 30 nM. Tozasertib induces apoptosis and autophagy. Phase 2. |
Senescence induction upon PKCι depletion combined with aurora kinase inhibition. ( a) MCF7 cells were transfected as above to deplete PKCι . Two days after transfection, cells were treated for the indicated time period with 400 n M VX-680. Medium with VX-680 was then removed and fresh medium was added. Cells were stained for SA-b -gal activity 5 days after the start of transfection.* indicates a P value <0.05. ( b) MCF7 cells were treated as above. Five days after transfection, cells were fixed and assessed for the presence of gH2AX foci by immunofluorescence microscopy. (c, d) MCF7 cells were treated with dimethyl sulfoxide (DMSO) control or 400 n M VX-680 for the indicated time periods. Total cell lysates were then analyzed by western blotting for levels of p21 and GAPDH (as loading control). A representative blot is shown in panel c. Quantitation of changes in p21 levels (normalized to vehicle-treated controls) is shown in panel d. The data shown are the means ±s.e. of three independent experiments. |
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| S1460 |
SP600125SP600125 (Nsc75890) is a broad-spectrum JNK inhibitor for JNK1, JNK2 and JNK3 with IC50 of 40 nM, 40 nM and 90 nM in cell-free assays, respectively; 10-fold greater selectivity against MKK4, 25-fold greater selectivity against MKK3, MKK6, PKB, and PKCα, and 100-fold selectivity against ERK2, p38, Chk1, EGFR etc. SP600125 is also a broad‐spectrum inhibitor of serine/threonine kinases including Aurora kinase A，FLT3 and TRKA with of IC50 of 60 nM, 90 nM and 70 nM. SP600125 inhibits autophagy and activates apoptosis. |
Loss of DUSP4 function upregulates IL-6 and IL-8 and enhances mammosphere growth. Immunoblot analysis of MDA-231 cells after treatment of 24 hours with 1 umol/L selumetinib (MEKi) or 10 umol/L SP600125 (JNKi). I, MDA-231 mammosphere formation quantitated by GelCount software 7 days after siRNA transfection. Where indicated, selumetinib (MEKi) or SP600125 (JNK1) or the combination was added to the mammosphere cultures.
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| S1147 |
Barasertib (AZD1152-HQPA)Defosbarasertib (AZD1152-HQPA, AZD2811, INH-34, Barasertib-HQPA) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, ~3700 fold more selective for Aurora B over Aurora A. Phase 1. |
Targeting PI3K, a common downstream effector of RTKs, with a selective inhibitor (GDC0941) sensitizes SOX10 knockdown cells to vemurafenib. shRNAs targeting SOX10 were introduced into A375 cells by lentiviral transduction. pLKO.1 empty vector served as a control vector (Ctrl). Cells were seeded in 6-well plates at the same density in the presence or absence of drug(s) at the indicated concentration. Cells were cultured for 2 weeks in the absence of vemurafenib or 4 weeks in the presence of vemurafenib before fixing and staining.
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| S1103 |
ZM 447439ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc. |
p31comet depletion delays MCC disassembly even with the proteasome inhibited. (A) FACS analysis of HeLa Tet-on cells transfected with control or p31comet siRNA and then treated with Taxol followed by Aurora B inhibition with ZM447439. The percentage of mitotic cells (cells that have 4N DNA content and are MPM2 positive) is shown for each sample. |
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| S1100 |
MLN8054MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM in Sf9 insect cell. It is more than 40-fold selective for Aurora A than Aurora B. Phase 1. |
Stacked column graphic representing the effect of the small molecule MLN8054 throughout oocyte developmental progress, namely during metaphase I, telophase I and metaphase II oocytes in different conditions. |
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| S1107 |
Danusertib (PHA-739358)Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib induces apoptosis, cell cycle arrest, and autophagy. Phase 2. |
Mice bearing subcutaneous allografts of conditional patched mutant tumor cells were treated twice weekly with vehicle (saline) or 30 mg/kg PHA-739358. (B)Images of tumors. (C) Tumor weights. Each point represents a single tumor, and grey lines represent mean tumor weights, which were significantly different between vehicle and PHA-739358 treated mice (p < 0.05, based on paired two-tailed t-test).
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| S1134 |
AT9283AT9283 is a potent JAK2/3 inhibitor with IC50 of 1.2 nM/1.1 nM in cell-free assays; also potent to Aurora A/B, Abl1(T315I). Phase 2. |
HEL cells were treated with 0.5, 1 or 5 uM of AT9283 or left untreated for 3 hrs. The expression and phosphorylation state of STAT5 (P-STAT5) and Jak2 (P-Jak2) was assessed by Western blot immunodetection.
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| S1249 |
JNJ-7706621JNJ-7706621 is pan-CDK inhibitor with the highest potency on CDK1/2 with IC50 of 9 nM/4 nM and showing >6-fold selectivity for CDK1/2 than CDK3/4/6 in cell-free assays. It also potently inhibits Aurora A/B and has no activity on Plk1 and Wee1. |
JNJ-7706621 treatment of tamoxifen-resistant cell lines leads to arrest in the G2 cell cycle phase. M phase cells from the upper right quadrants were quantified relative to total G2/M phase cells. Statistical significant differences from vehicle-treated cells are denoted by asterisks; *P<0.05, **P<0.01.
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| S1529 |
HesperadinHesperadin potently inhibits Aurora B with IC50 of 250 nM in a cell-free assay. It markedly reduces the activity of AMPK, Lck, MKK1, MAPKAP-K1, CHK1 and PHK while it does not inhibit MKK1 activity in vivo. |
HeLa cells treated with nocodazole containing DMSO or Hesperadin (100 nM) for 2 h and stained with the indicated antibodies. |
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| S1451 |
Aurora A Inhibitor I (TC-S 7010)Aurora A Inhibitor I (TC-S 7010) is a novel, potent, and selective inhibitor of Aurora A with IC50 of 3.4 nM in a cell-free assay. It is 1000-fold more selective for Aurora A than Aurora B. Aurora A Inhibitor I (TC-S 7010) triggers apoptosis through the ROS-mediated UPR signaling pathway. |
Aurora-A inhibitors severely impair neuronal migration. Migration of granular neurons after treatment of Aurora-A inhibitors was examined. a, Western blotting analysis of proteins or phosphorylated proteins. Aurora-A and NDEL1 displayed similar expression levels, whereas phosphorylated Aurora-A and NDEL1 proteins were decreased during treatment with Aurora-A inhibitors. Relative intensities of the bands of Western blotting are displayed at the bottom. |
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| S2158 |
KW-2449KW-2449 is a multiple-targeted inhibitor, mostly for Flt3 with IC50 of 6.6 nM, modestly potent to FGFR1, Bcr-Abl and Aurora A; little effect on PDGFRβ, IGF-1R, EGFR. Phase 1. |
Western blot analysis of p-histone and histone. 0-10μM KW2449 was added.
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| S1154 |
SNS-314SNS-314 Mesylate is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively. It is less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2. Phase 1. |
Nuclear morphology and cell cycle distribution (green for phases G2/M, and red for phase G1) of NMuMG-Fucci cells exposed to 1 uM SNS-314 for 96 h.
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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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| S1454 |
PHA-680632PHA-680632 is potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, respectively. It has 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, and VEGFR2/3. |
Quantification of phT288-AURKA expression as in figure n=3, normalized to total AURKA and plotted as relative intensity units (RIU) +/- S.E.M. Two-way ANOVA, p<0.0001, (shCon/shN1 or shN2), p=0.0013 (shN1/shN2).
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| S2770 |
MK-5108 (VX-689)MK-5108 (VX-689) is a highly selective Aurora A inhibitor with IC50 of 0.064 nM in a cell-free assay and is 220- and 190-fold more selective for Aurora A than Aurora B/C, while it inhibits TrkA with less than 100-fold selectivity. MK-5108 (VX-689) induces autophagy. Phase 1. |
-S277001W0220130927.gif)
-S277001W0220130927.gif)
MK-5108 specifically inhibits AURKA and delays mitotic exit. (a) MK-5108 inhibits AURKA but not AURKB. Mitotic HeLa cells were obtained by exposure to nocodazole for 16 h followed by mechanical shake off. The cells were incubated with the indicated concentrations of MK-5108 for 2 h. Nocodazole and MG132 were included to prevent mitotic exit. Lysates were then prepared and activated phospho-AURKAThr288 and AURKBThr232 were detected with immunoblotting. Uniform loading was confirmed by immunoblotting for actin. (b) MK-5108 prevents activation of AURKA but not AURKB. HeLa cells were incubated with the indicated concentrations of MK-5108 for 8 h. Nocodazole was then added for another 6 h to trap any cells that entered mitosis. Mitotic cells were isolated by mechanical shake off. Lysates were prepared and analyzed with immunoblotting. Actin analysis was included to assess loading and transfer. (c) MK-5108 induces a G 2 /M delay. HeLa cells were treated with the indicated concentrations of MK-5108 for 24 h. DNA contents were analyzed with flow cytometry. |
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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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| S2719 |
AMG-900AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor for Aurora A/B/C with IC50 of 5 nM/4 nM /1 nM. It is >10-fold selective for Aurora kinases than p38α, Tyk2, JNK2, Met and Tie2. Phase 1. |
AURK inhibitors have significant cytotoxic effect on PCa cells. The cytotoxic effects of the AURK inhibitors were measured by MTS assay after 72 h treatment with these inhibitors. The viability fraction was compared to the untreated cells for each cell line. Error bars represent the SEM. C. Relative cell vability of PCa cells treated with AMG 900 at the concentrations of 0.05, 0.25 and 1.25 μmol/l. |
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| S1519 |
CCT129202CCT129202 is an ATP-competitive pan-Aurora inhibitor for Aurora A, Aurora B and Aurora C with IC50 of 0.042 μM, 0.198 μM and 0.227 μM, respectively. It is less potent to FGFR3, GSK3β, PDGFRβ, etc. |
T47D Breast cancer cells were pretreated with p-Aurora, Aurora and then treated with the indicated concentrations of CCT129202.
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| S2740 |
GSK1070916GSK1070916 is a reversible and ATP-competitive inhibitor of Aurora B/C with IC50 of 3.5 nM/6.5 nM. It displays >100-fold selectivity against the closely related Aurora A-TPX2 complex. Phase 1. |
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| S2718 |
TAK-901TAK-901 is a novel inhibitor of Aurora A/B with IC50 of 21 nM/15 nM. It is not a potent inhibitor of cellular JAK2, c-Src or Abl. Phase 1. |
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| S2744 |
CCT137690CCT137690 is a highly selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 15 nM, 25 nM and 19 nM. It has little effect on hERG ion-channel. |
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| S7065 |
MK-8745MK-8745 is a potent and selective Aurora A inhibitor with IC50 of 0.6 nM, more than 450-fold selectivity for Aurora A over Aurora B. |
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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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| S8699 |
SNS-314 MesylateSNS-314 Mesylate is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively and less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2. |
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| S8782 |
LY3295668LY3295668 (AK-01) is a potent, orally active and specific inhibitor of Aurora A kinase with Ki of 0.8 nM and 1038 nM for AURKA and AURKB, respectively. |
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| S2931 |
Aurora Kinase Inhibitor IIIAurora kinase inhibitor III is a potent inhibitor of Aurora A kinase with an IC50 of 42 nM and has high selectivity for Aurora A over BMX, BTK, IGF-1R, c-Src, TRKB, SYK, and EGFR (IC50s = 386, 3,550, 591, 1,980, 2,510, 887, and >10,000 nM, respectively). |
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| S7588 |
ReversineReversine is a potent human A3 adenosine receptor antagonist with Ki of 0.66 μM, and a pan-aurora A/B/C kinase inhibitor with IC50 of 12 nM/13 nM/20 nM, respectively. Also used for stem cell dedifferentiation. |
Immunofluorescence of acetylated a-tubulin (red) in control (a), reversin-treated (b), and BI 2536/Reversin mixture-treated embryos (c).The embryos treated with Reversine completed first mitosis, but the nuclei of their blastomeres were fragmented (b, arrows). Embryos inhibited withthe BI 2536/Reversine mixture arrested before the onset of anaphase. Microtubules of the spindle are disorganized (c, double-arrow) and thechromosomes are misaligned (c, arrows) in these inhibited embryos. DNA is counter-stained with DAPI (blue). Scale bar, 10 μm. |
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| S9658 |
SP-96SP-96 is a potent, selective and non-ATP-competitive inhibitor of Aurora B with IC50 of 0.316 nM. SP-96 can be used for the research of triple negative breast cancer (TNBC). |
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| S6214 |
H-1152 dihydrochlorideH-1152 dihydrochloride (2HCl) is a membrane-permeable and selective inhibitor of Rho-associated protein kinase (ROCK). H-1152 inhibits ROCK2, PKA, PKC, PKG, AuroraA and CaMK2 with IC50 of 0.0120 μM, 3.03 μM, 5.68 μM, 0.360 μM, 0.745 μM and 0.180 μM, respectively. |
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| S7843 |
BI-847325BI-847325 is an orally bioavailable, and selective dual MEK/Aurora kinase inhibitor with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM for Xenopus laevis Aurora B, human Aurora A and Aurora C, as well as human MEK1 and MEK2, respectively. Phase 1. |
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| S1272 |
XL228XL228 is a protein kinase inhibitor with IC50 of 5 nM, 1.4 nM, 3.1 nM, 1.6 nM, 6.1 nM and 2 nM for wild-type ABL kinase, ABL T315I, Aurora A, IGF-1R, SRC and LYN, respectively. |
