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受注：045-509-1970 |
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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder |
| 化学式 | C23H22FN3O3.2HCl |
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| 分子量 | 480.36 | CAS No. | 1360460-82-7 | |
| Solubility (25°C)* | 体外 | Water | 96 mg/mL (199.85 mM) | |
| DMSO | 48 mg/mL (99.92 mM) | |||
| Ethanol | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Anlotinib (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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| in vitro | Anlotinib occupies the ATP-binding pocket of VEGFR2 tyrosine kinase and shows high selectivity and inhibitory potency (IC 50 <1 nmol/L) for VEGFR2 relative to other tyrosine kinases. Anlotinib inhibits VEGFR2 and VEGFR3 with IC50 values of 0.2 and 0.7 nmol/L, respectively. The inhibitory potency of anlotinib against VEGFR1 is lower, with an IC50 value of 26.9 nmol/L. The IC50 values of anlotinib for inhibition of the PDGFR-related kinases c-Kit and PDGFRβ are 14.8 and 115.0 nmol/L, respectively. Anlotinib has little effect on the activity of other kinases, including c-Met, c-Src, EGFR and HER2, even at a concentration of 2000 nmol/L. Anlotinib inhibits VEGF-induced signaling and cell proliferation in HUVEC with picomolar IC50 values. However, micromolar concentrations of anlotinib are required to inhibit tumor cell proliferation directly in vitro. Anlotinib significantly inhibits HUVEC migration and tube formation; it also inhibits microvessel growth from explants of rat aorta in vitro[1]. |
| in vivo | Anlotinib decreases vascular density in tumor tissue in vivo. Compared with the well-known tyrosine kinase inhibitor sunitinib, once-daily oral dose of anlotinib shows broader and stronger in vivo antitumor efficacy and, in some models, causes tumor regression in nude mice. It is well-tolerated in mice. Anlotinib is efficacious at doses (1.5‐6 mg/kg daily) that are significantly lower than effective doses of other TKI, which require doses of 20‐100 mg/kg to achieve significant inhibition of tumor growth in mice[1]. In vivo, anlotinib has showed broad activity against human tumor xenograft models of the colon (SW-620), ovarian (SK-OV-3), liver (SMMC-7721), renal (Caki-1), glioma (U87MG), and non-small cell lung (Calu-3) during dosing period. In Sprague-Dawley rats and beagle dogs, anlotinib is rapidly absorbed from the gastrointestinal tracks after oral administration. The oral bioavailability is 23-45 % in rats and 47-74 % in dogs. Anlotinib exhibits large volume of distribution in both species. In rats, primary tissues, such as the lung, kidneys, liver, and heart, exhibit significant higher exposure levels to anlotinib compared with that in plasma. The exposure level in the brain is comparable with the corresponding plasma level. In tumor-bearing mice, anlotinib concentrates 2.4-2.6 times in tumor tissue than in plasma. In human, anlotinib exhibits a quite long t1/2 (96 ± 17 h), which appeared to be dose-independent[2]. The terminal half-life of anlotinib in dogs (22.8±11.0 h) is longer than that in rats (5.1±1.6 h). This difference appeares to be mainly associated with an interspecies difference in total plasma clearance (rats, 5.35±1.31 L/h/kg; dogs, 0.40±0.06 L/h/kg). In human plasma, anlotinib is predominantly bound to albumin and lipoproteins, rather than to α1-acid glycoprotein or γ-globulins[3]. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Enzyme-linked immunosorbent assay | |
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| Inhibitory activity of anlotinib against tyrosine kinases was determined using ELISA. Reaction of ATP with tyrosine kinase was initiated in reaction buffer (50 mmol/L HEPES pH 7.4, 50 mmol/L MgCl2, 0.5 mmol/L MnCl2, 0.2 mmol/L Na3VO4, 1 mmol/L DTT) and incubated for 1 hour at 37°C in 96-well plates precoated with 20 μg/mL Poly(Glu,Tyr)4:1. The plate was incubated with PY99 antibody and then with HRP-conjugated anti-mouse IgG. After reaction with o-phenylenediamine solution and then termination with the addition of 2N H2SO4, absorbance was measured at 490 nm using a Synergy H4 Hybrid reader. | ||
| 細胞アッセイ | 細胞株 | HUVEC, Mo7e, U-87MG and A431 cells |
| 濃度 | 0-10 μM | |
| 反応時間 | 1.5 h | |
| 実験の流れ | Serum-starved HUVEC, Mo7e, U-87MG and A431 cells are treated with different concentrations of test agents for 1.5 h and then stimulated with vascular endothelial growth factor (VEGF; 20 ng/mL), stem cell factor-1 (SCF-1; 2.5 ng/mL), platelet-derived growth factor-BB (PDGF-BB; 10 ng/mL), or epidermal growth factor (EGF; 10 ng/mL) for 10 min, respectively. Cell lysates are probed with the indicated antibodies. |
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| 動物実験 | 動物モデル | human colon cancer SW620 xenograft model（Balb/cA-nude mice, 5-6 weeks old) |
| 投薬量 | 0.75, 1.5, 3 and 6 mg/kg | |
| 投与方法 | oral | |
参考
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Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Genomic and transcriptomic profiling of peripheral T cell lymphoma reveals distinct molecular and microenvironment subtypes [ Cell Rep Med, 2024, 5(2):101416] | PubMed: 38350451 |
| Inhibition of anlotinib-induced autophagy attenuates invasion and migration by regulating epithelial-mesenchymal transition and cytoskeletal rearrangement through ATG5 in human osteosarcoma cells [ Braz J Med Biol Res, 2024, 57:e13152] | PubMed: 38381883 |
| The function and mechanism of PSMD14 in promoting progression and resistance to anlotinib in osteosarcoma [ Cancer Cell Int, 2023, 23(1):309] | PubMed: 38053170 |
| Novel structured ADAM17 small-molecule inhibitor represses ADAM17/Notch pathway activation and the NSCLC cells' resistance to anti-tumour drugs [ Front Pharmacol, 2023, 14:1189245] | PubMed: 37456760 |
| Tocilizumab (monoclonal anti-IL-6R antibody) reverses anlotinib resistance in osteosarcoma [ Front Oncol, 2023, 13:1192472] | PubMed: 37404767 |
| Dihydroartemisinin Potentiates VEGFR-TKIs Antitumorigenic Effect on Osteosarcoma by Regulating Loxl2/VEGFA Expression and Lipid Metabolism Pathway [ J Cancer, 2023, 14(5):809-820] | PubMed: 37056396 |
| PI3K inhibitor impairs tumor progression and enhances sensitivity to anlotinib in anlotinib-resistant osteosarcoma [ Cancer Lett, 2022, 536:215660] | PubMed: 35318116 |
| Targeting ADRB2 enhances sensitivity of non-small cell lung cancer to VEGFR2 tyrosine kinase inhibitors [ Cell Death Discov, 2022, 8(1):36] | PubMed: 35075132 |
| A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs [ Front Pharmacol, 2022, 13:895744] | PubMed: 35662712 |
| miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway [ J Cancer, 2022, 13(15):3660-3673] | PubMed: 36606198 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。