RMC5127 is an orally available, mutation-selective RAS G12V inhibitor exhibiting central nervous system (CNS) and brain permeability. It suppresses the RAS pathway and induces apoptosis in KRAS G12V mutant cancer cells, demonstrating antitumour activity.

In a panel of human cancer cell lines harboring the KRASG12V mutation, RMC5127 significantly suppressed RAS pathway activity, inhibited cell proliferation, and induced cell apoptosis; however, in a panel of K/N/HRAS wild-type cancer cell lines, this drug only exerted a submaximal inhibitory effect [1].

Following repeated oral administration of RMC5127 to subcutaneous cell line-derived xenograft (CDX) models and patient-derived xenograft (PDX) models of non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC) harboring the KRASG12V mutation, significant and durable antitumor activity was observed. In the whole brain tissues of naïve mice (tumor-free mice), dose-dependent exposure of RMC5127 was detected, indicating that this compound possesses blood-brain barrier penetration ability [1].