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MRTX1133
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
MRTX1133图片
CAS NO:2621928-55-8
包装与价格:
包装价格(元)
5mg电议
10mg电议

产品介绍
MRTX1133 是一种非共价、有效和选择性的 KRAS G12D 抑制剂。 MRTX1133 以最佳方式填充开关 II 口袋并延伸三个取代基以有利地与蛋白质相互作用,导致对 KRAS G12D 的估计 KD 为 0.2 pM。 MRTX1133 阻止 SOS1 催化的核苷酸交换和/或 KRAS G12D/GTP/RAF1 复合物的形成,从而抑制突变的 KRAS 依赖性信号转导。 MRTX1133 选择性抑制 KRAS G12D 突变体,但不抑制 KRAS 野生型肿瘤细胞。 MRTX1133 在细胞试验中具有个位数的纳摩尔活性,并且在含有 KRAS G12D 突变的肿瘤模型中具有显着的体内功效。
Cas No.2621928-55-8
分子式C33H31F3N6O2
分子量600.63
储存条件Store at -20°C
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

MRTX1133 is an exceptionally potent and selective KRASG12D inhibitor with high affinity (<2nM).[1]

In vitro, in the AGS cell line, MRTX1133 inhibited ERK phosphorylation with an IC50of 2 nM. In the meanwhile, MRTX1133 was against the same cell line with an IC50of 6 nM in a 2D viability assay.[1]In vitro efficacy test, in KRASG12D–mutant HPAC Cells, it indicated that treatment with 0.05 nM - 300 nM MRTX1133 has a dose-dependent pERK, pS6 & DUSP6 modulation.[2]

In vivo experiment it shown that treatment with 30 mg/kg of MRTX1133 intraperitoneally in CD-1 mice caused the sustained plasma exposure exceeding the free-fraction-adjusted pERK IC50value in the KRASG12D mutant Panc 04.03 cell line for approximately 8 h. And in the Panc 04.03 xenograft tumor model, it suggested that MRTX1133 (3-30 mg/kg, i.p.) has 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.[1]

References:
[1].Wang X, Allen S, et al. Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor. J Med Chem. 2022 Feb 24;65(4):3123-3133.
[2].Swiatnicki M, Engel L, Shrestha R, Alves J, Goueli SA, Zegzouti H. Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay. SLAS Discov. 2022 Jun;27(4):249-257.