MRTX849 是一种有效，口服可用，突变选择性的 KRAS G12C 共价抑制剂，具有潜在抗肿瘤活性的。MRTX849 在半胱氨酸 12 残基处与 KRAS G12C 共价结合，将蛋白锁定在非活性的 GDP 结合构象中，并抑制 KRAS 依赖性信号转导。
货号:ajcx14750
CAS:2326521-71-3
分子式:C32H35ClFN7O2
分子量：604.12
溶解度:DMSO: 25 mg/mL (41.38 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

MRTX849 is a potent, orally-available, and mutation-selective covalent inhibitor of KRAS G12C with potential antineoplastic activity. MRTX849 covalently binds to KRAS G12C at the cysteine at residue 12, locks the protein in its inactive GDP-bound conformation, and inhibits KRAS-dependent signal transduction[1][2].

In cell lines, MRTX849 inhibits growth and viability of cells harboring KRASG12C mutations, but not in cells with other mutant forms or of wild-type KRAS[2].

MRTX849 inhibits KRASG12C signaling in cell lines harboring this mutation, and results in tumor regression in a broad spectrum of KRASG12C animal models[2].

[1]. Christensen JG, et al. The KRASG12C Inhibitor, MRTX849, Provides Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers in Mouse Models and Patients. Cancer Discov. 2019 Oct 28. pii: CD-19-1167. [2]. Kyriakos P. Papadopoulos, et al. A phase I/II multiple expansion cohort trial of MRTX849 in patients with advanced solid tumors with KRAS G12C mutation. Journal of Clinical Oncology 2019 37:15_suppl, TPS3161-TPS3161.