2765082-12-8

生物活性：RMC-7977 是一种具有口服活性的三复合 RAS 抑制剂，可同时结合亲环蛋白 A (CYPA) (K_d = 195 nM) 和 KRAS (G12V) (K_d = 292 μM)，对 KRAS、NRAS 和 HRAS 三种 RAS 蛋白及其各种野生型和突变型变体具有广谱抑制活性。RMC-7977 通过抑制 ERK、CRAF和 RSK 磷酸化以及增加 PARP 剪切来诱导细胞凋亡 (Apoptosis)，可导致肿瘤消退，减少 KRAS^G12C 癌症模型的耐药性，并且在多种 RAS 癌症模型中具有良好的耐受性^[1][2][3]。

RMC-7977 is an orally active triple-complex RAS inhibitor that can simultaneously bind to cyclophilin A (CYPA) (K_d = 195 nM) and KRAS (G12V) (K_d = 292 μM). It exhibits broad-spectrum inhibitory activity against KRAS, NRAS, and HRAS proteins and their various wild-type and mutant variants. RMC-7977 induces apoptosis by inhibiting the phosphorylation of ERK, CRAF, and RSK, as well as increasing PARP cleavage. This leads to tumor regression, reduces resistance in KRAS^G12C cancer models, and demonstrates good tolerability across various RAS cancer models^[1][2][3].