产品说明书
BI-3406
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同义名 : | SOS1-IN-2 |
| CAS号 : | 2230836-55-0 | |
| 货号 : | A1177157 | |
| 分子式 : | C23H25F3N4O3 | |
| 纯度 : | 99%+ | |
| 分子量 : | 462.465 | |
| MDL号 : | MFCD32197204 | |
| 存储条件： |
粉末 Keep in dark place,Sealed in dry,2-8°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 105 mg/mL(227.04 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO 无水乙醇: 100 mg/mL(216.23 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇 |
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| 动物实验配方： |
| 生物活性 | |||
|---|---|---|---|
| 描述 | Son of Sevenless (SOS) is a guanine nucleotide exchange factor that activates the important cell signaling switch KRAS. SOS acts as a pacemaker for KRAS, the beating heart of cancer, by catalyzing the "beating" from the KRAS(off) to the KRAS(on) conformation[1]. BI-3406 is an orally active, highly potent and selective between KRAS and Son of Sevenless 1 (SOS1) interaction inhibitor (IC50: 6 nM), with anticancer activity. BI-3406 does not block the interaction of KRAS with SOS2 but elicits activity on a broad panel of KRAS oncogenic variants, including all major G12 and G13 oncoproteins. In KRAS-dependent cancers, BI-3406 potently reduces the formation of GTP-loaded KRAS, and inhibits MAPK pathway signaling. Down-modulation of this signaling cascade by BI-3406 in KRAS G12 or G13 mutant cells effectively limits cell proliferation[2]. BI-3406 inhibits SOS1 catalyzed formation of GTPKRAS in KRAS-mutant cells (IC50 = 83-231 nM), inhibits downstream signaling (pERK IC50 = 17-57nM), and inhibits proliferation in anchorage-independent 3D growth assays (IC50 = 16-52 nM) in a range of KRASmutant cells[1]. BI-3406 is an orally bioavailable compound and single administration was sufficient to reduce RAS-GTP and pERK levels in A549 xenograft tumors over a period of 24 hours and 7 hours, respectively. At a dose of 50 mg/kg bid, relevant levels of unbound exposures are achieved for the first 12 hours, when compared to unbound IC50 levels in A549 cells. In MIA PaCa-2 tumor bearing mice, twice daily compound treatment with 50 mg/kg BI-3406 resulted in pathway modulation over a period of up to 10 hours[3]. | ||
| 实验方案 | |||
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| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.16mL 0.43mL 0.22mL |
10.81mL 2.16mL 1.08mL |
21.62mL 4.32mL 2.16mL |
| 参考文献 |
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