TAK-632CAS号: 1228591-30-7分子式: C27H18F4N4O3S分子量: 554.52描述纯度储存/保存方法别名外观可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)
产品描述 | |
描述 |
TAK-632 is a selective pan-RAF kinase inhibitor with IC50 values of 2.4/1.4 nM for BRAF V600E/c-RAF; > 60 fold selectivity over VEGFR. |
纯度 |
>98%
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储存/保存方法 |
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
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基本信息 | |
别名 |
TAK 632; TAK632
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外观 |
Powder
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可溶性/溶解性 |
DMSO 100 mg/mL (180.33 mM)
Ethanol 2 mg/mL (3.6 mM) |
生物活性 | |
靶点 |
C-Raf ,B-Raf ,Aurora B ,PDGFRβ ,FGFR3
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In vitro(体外研究) |
TAK-632 inhibits phosphorylation of MEK and ERK in melanoma A375 cells (BRAFV600E) with IC50 of 12 nM and 16 nM, respectively. In human melanoma HMVII cells (NRASQ61K/BRAFG469V), TAK-632 also shows strong inhibition of pMEK and pERK with IC50 of 49 nM and 50 nM, respectively. Moreover, TAK-632 also exhibits antiproliferative activity in both A375 and HMVII cells with GI50 of 66 nM and 200 nM, respectively. TAK-632 induces RAF dimerization but inhibits the kinase activity of the RAF dimer because of its slow dissociation from RAF. The combination of TAK-632 and TAK-733 exhibits synergistic antiproliferative effects in BRAF- and NRAS-mutated melanoma cells.
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In vivo(体内研究) |
TAK-632 shows superior oral bioavailability in both rats and dogs. TAK-632 (3.9–24.1 mg/kg, p.o.) exhibits dose-dependent antitumor efficacy without severe body weight reduction in a melanoma A375 (BRAFV600E) xenograft model and a human melanoma HMVII (NRASQ61K/BRAFG469V) xenograft in rats. In NRAS-mutant melanoma SK-MEL-2 xenograft model, TAK-632 (60 or 120 mg/kg, p.o.) also exhibits potent antitumor efficacy without severe toxicity.
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分子结构图