MRTX0902 是一种口服有效的SOS1的抑制剂，IC50为 46 nM。
| 生物活性 | MRTX0902 is an orally active and potentSOS1inhibitor with anIC50of 46 nM (WO2021127429A1; Example 12-10)[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | MRTX0902 (compound 32) (1 μM; 0, 2, 4, 8, 15, and 30 minutes) shows a moderate Clintvalue of 195 mL/min/kg in human liver microsome and a low lipophilicity with cLogP of 3.4[1].
MRTX0902 displays high selectivity on SOS1 (Ki=2 nM) over SOS2 and EGFR (both Kivalues >10,000 nM), MRTX0902 inhibits MKN1 cells with an IC50value of 29 nM[1].
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体内研究
(In Vivo) | MRTX0902 (compound 32) (25, 50 mg/kg; p.o.; twice daily; 25 d) shows anti-tumor effect in mouse model and results tumor regression[1].
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[1].
PK Parameters for MRTX0902 across Species[1]
| Parameter | Route | Dose (mg/kg) | Cl (mL/min/kg) | Vd,ss(L/kg) | T1/2(iv) (h) | F (%) | | Mouse | IV/PO | 3/30 | 4.4 | 0.28 | 1.3 | 69 | | Rat | IV/PO | 1/10 | 14.6 | 0.28 | 0.62 | 83 | | Dog | IV/PO | 2/10 | 7.6 | 0.48 | 0.86 | 38 |
| Animal Model: | Female CD-1 mice[1] | | 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[1] | | 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. |
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| Clinical Trial | |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 12.5 mg/mL(32.18 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 2.5742 mL | 12.8710 mL | 25.7420 mL | | 5 mM | 0.5148 mL | 2.5742 mL | 5.1484 mL | | 10 mM | 0.2574 mL | 1.2871 mL | 2.5742 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 1.25 mg/mL (3.22 mM); Clear solution
此方案可获得 ≥ 1.25 mg/mL (3.22 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
*以上所有助溶剂都可在本网站选购。 |
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