MRTX849

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MRTX849 是一种有效的、选择性的共价 KRASG12C 抑制剂，具有潜在的抗肿瘤活性。选择性修饰 GDP 结合的 KRASG12C 中的突变半胱氨酸 12，并抑制 KRAS 依赖性信号传导。

MRTX849 is a potent selective and covalent KRASG12C inhibitor with potential antineoplastic activity.selectively modifies mutant cysteine 12 in GDP-bound KRASG12C and inhibits KRAS-dependent signaling.

Cell Viability Assay Cell Line:MIA PaCa-2, H1373, H358, H2122, SW1573, H2030, KYSE-410 cells (G12C); H1299 (WT); A549 (G12S), HCT116 (G13D) cellsConcentration:0.1, 1, 10, 100, 1000, 10000 nM Incubation Time:24 hours Result:Inhibits cell growth in the vast majority of KRAS G12C-mutant cell lines with IC50 values ranging between 10 and 973 nM in the 2D format and between 0.2 and 1042 nM in the 3D format.Western Blot AnalysisCell Line:MIA PaCa-2 cells Concentration:0.24, 0.5, 1.0, 2.0, 3.9, 7.8, 15.6, 31.3, 62.5, 125, 250, 500, 1000 nM Incubation Time:24 hours Result:Inhibits KRAS-dependent signaling targets including ERK1/2 phosphorylation (Thr202/Tyr204 ERK1; pERK), S6 phosphorylation (RSK-dependent Ser235/236; pS6) and expression of the ERK-regulated DUSP6, each with IC50s in the single-digit nanomolar range in cell lines.

Animal Model:MIA PaCa-2 model (6-8-week-old, female, athymic nude-Foxn1 nu mice)Dosage:1, 3, 10, 30 and 100 mg/kg Administration:Oral gavage; daily until Day 16Result:Rapid tumor regression was observed at the earliest posttreatment tumor measurement and animals in the 30 and 100 mg/kg cohorts exhibited evidence of a complete response at study Day 15. Dosing was stopped at study Day 16 and all 4 mice in the 100 mg/kg cohort and 2 out of 7 mice in the 30 mg/kg cohort remained tumor-free through study Day 70.

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MAPK/ERK Signaling

Ras

KRAS G12C

cancer

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2326521-71-3

604.12

C32H35ClFN7O2

>98% (HPLC)

DMSO:100 mg/mL (165.53 mM; Need ultrasonic)

CN1CCC[C@H]1COc1nc2CN(CCc2c(n1)N1CCN([C@@H](CC#N)C1)C(=O)C(F)=C)c1cccc2cccc(Cl)c12

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(-20℃)

With Ice Pack

≥ 2 years