MRTX1133

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

MRTX1133 是一种有效的、选择性的、非共价 KRASG12D 抑制剂。它在细胞分析中具有皮摩尔结合亲和力和个位数纳摩尔活性。此外，它在含有 KRASG12D 突变的肿瘤模型中具有显着的体内疗效。

MRTX1133 is a potent, selective, noncovalent KRASG12D inhibitor. It has picomolar binding affinity, single-digit nanomolar activity in cellular assays. In addition, it has significant in vivo efficacy in tumor models harboring KRASG12D mutations.

MRTX1133 inhibits ERK phosphorylation in the AGS cell line with an IC50 ranging 1-10 nM (AsPC-1, Panc 04.03, Panc 02.03, SW1990, GP2D, Suit2, A427, SNU1033, and HPAC cells). In a 2D viability assay, the IC50 of MRTX1133 is 6 nM against AGS cells (KRAS G12D), while demonstrating more than 500-fold selectivity against MKN1, a cell line which is dependent on KRAS for its growth and survival due to the amplification of wild-type KRAS.

MRTX1133 displays efficacious in a KRAS G12D mutant xenograft mouse tumor model. Animal Model:6-8-weekold, female, athymic nude-Foxn1nu mice (Panc 04.03 model)Dosage:3, 10, or 30 mg/kg Administration: aperitoneal; twice a day for 28 days Result:An antitumor efficacy study in this model resulted in MRTX1133 dose-dependent antitumor activity with 94% growth inhibition observed at 3 mg/kg BID (IP) and tumor regressions of -62% and -73% observed at 10 and 30 mg/kg BID (IP), respectively.

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MAPK/ERK Signaling

Ras

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2621928-55-8

600.63

C33H31F3N6O2

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (83.25 mM)

C#Cc1c2c(-c(ncc(c3n4)c(N5CC(CC6)NC6C5)nc4OC[C@](CCC4)(C5)N4C[C@@H]5F)c3F)cc(O)cc2ccc1F

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(-20℃)

With Ice Pack

≥ 2 years