MRTX1133

Research use only, not for human use.

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 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