| 產(chǎn)品描述： | TAK-632 is a potent pan-RAF inhibitor with IC50 of 1.4, 2.4 and 8.3 nM for CRAF, BRAFV600E, BRAFWT, respectively. |
| 靶點(diǎn)： |
c-Raf:1.4 nM (IC50);Braf:8.3 nM (IC50);Aurora B:66 nM (IC50);PDGFRβ:120 nM (IC50);PDGFRα:610 nM (IC50);FGFR3:280 nM (IC50);TIE2:740 nM (IC50);IKKβ:3700 nM (IC50);CDK1:790 nM (IC50);CDK2:580 nM (IC50);p38α:600 nM (IC50);GSK3β:500 nM (IC50);MEK1:3700 nM (IC50);Raf;?FGFR;?PDGFR;?AuroraKinase |
| 體內(nèi)研究： |
TAK-632 demonstrates dramatically improved solubility (740 μg/mL) in pH 6.8 phosphate buffer and exhibits significant oral absorption (at a dose of 25 mg/kg, AUC, 32.47 μg h/mL; F, 51.7%) in rats. In a dog PK study, 10 mg/kg administration of TAK-632 also shows superior oral bioavailability (F: 108%).Oral single administration of TAK-632 inhibits pERK in tumors at 8 h after its administration over a dose range of 1.9-24.1 mg/kg. In particular, 9.7-24.1 mg/kg dosing with TAK-632 strongly inhibits pERK levels to 11% of the control. TAK-632 exhibits dose-dependent antitumor efficacy without severe body weight reduction over a dose range of 3.9-24.1 mg/kg. Significant tumor regression is observed at 9.7 mg/kg and 24.1 mg/kg (T/C=?2.1% and ?12.1%, respectively). TAK-632 exhibits potent antitumor efficacy when orally administered at 60 mg/kg once daily (T/C=37%, P<0.001) or at 120 mg/kg once daily (T/C=29%, P<0.001) for 21 days without severe toxicity in NRAS-mutant melanoma using a SK-MEL-2 xenograft model |
| 參考文獻(xiàn)： |
1. Okaniwa M, et al. Discovery of a selective kinase inhibitor (TAK-632) targeting pan-RAF inhibition: design, synthesis, and biological evaluation of C-7-substituted 1,3-benzothiazole derivatives. J Med Chem. 2013 Aug 22;56(16):6478-94. 2. Nakamura A, et al. Antitumor activity of the selective pan-RAF inhibitor TAK-632 in BRAF inhibitor-resistant melanoma. Cancer Res. 2013 Oct 11. |
| 溶解性： |
DMSO : 100 mg/mL (180.34 mM; Need ultrasonic) |
| 保存條件： |
2-8℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.803 ml |
9.017 ml |
18.034 ml |
| 5 mM |
0.361 ml |
1.803 ml |
3.607 ml |
| 10 mM |
0.18 ml |
0.902 ml |
1.803 ml |
| 50 mM |
0.036 ml |
0.18 ml |
0.361 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
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危險品化學(xué)品經(jīng)營許可證（不帶存儲）
營業(yè)執(zhí)照(三證合一)
北京