| 產(chǎn)品描述： | MRTX0902 is an orally active and potent SOS1 inhibitor with an IC50 of 46 nM (WO2021127429A1; Example 12-10) |
| 靶點(diǎn)： |
KRAS-SOS1:46 nM (IC50);Raf |
| 體外研究： |
MRTX0902 (compound 32) (1 μM; 0, 2, 4, 8, 15, and 30 minutes) shows a moderate Clint value of 195 mL/min/kg in human liver microsome and a low lipophilicity with cLogP of 3.4.
MRTX0902 displays high selectivity on SOS1 (Ki=2 nM) over SOS2 and EGFR (both Ki values >10,000 nM), MRTX0902 inhibits MKN1 cells with an IC50 value of 29 nM. |
| 體內(nèi)研究： |
MRTX0902 (compound 32) (25, 50 mg/kg; p.o.; twice daily; 25 d) shows anti-tumor effect in mouse model and results tumor regression. MRTX0902 (1-3 mg/kg for i.v. or 10-30 mg/kg for p.o.; single dose) exhibits good brain penetrance, low clearance, and high bioavailability. Animal Model: Female CD-1 mice Dosage: 50 mg/kg Administration: Oral gavage; twice daily; 1 day Result: Resulted free drug exposure in the brain as well as the efflux ratio in the Caco-2 assay (ER = 1.5).Showed short half-life of the compound in mice (T1/2 = 1.3 h). Animal Model: MIA PaCa-2 xenograft model in mouse Dosage: 25 mg/kg; 50 mg/kg Administration: Oral gavage; twice daily; 25 days Result: Reduced tumor growth by 41% and 53% at 25 mg/kg and 50 mg/kg administration. |
| 參考文獻(xiàn)： |
1. Ketcham JM, et al. Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein-Protein Interaction. J Med Chem. 2022 Jul 28;65(14):9678-9690. |
| 溶解性： |
soluble in DMSO |
| 保存條件： |
-20°C |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.574 ml |
12.871 ml |
25.742 ml |
| 5 mM |
0.515 ml |
2.574 ml |
5.148 ml |
| 10 mM |
0.257 ml |
1.287 ml |
2.574 ml |
| 50 mM |
0.051 ml |
0.257 ml |
0.515 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(xiǎn)品化學(xué)品經(jīng)營許可證（不帶存儲(chǔ)）
營業(yè)執(zhí)照(三證合一)
北京