calderasib

Calderasib is an oral, covalent, mutant-selective small-molecule inhibitor of Kirsten rat sarcoma viral oncogene homolog bearing the G12C mutation (KRAS G12C), designed to irreversibly bind the mutant cysteine in the switch-II pocket and shut down downstream MAPK/ERK signaling. Preclinical data show nanomolar inhibition of KRAS G12C–driven signaling, strong phospho‑ERK suppression, and antitumor activity in KRAS G12C–mutant xenograft models, and the agent is in early clinical development for advanced solid tumors harboring KRAS G12C mutations, including non–small cell lung cancer and other solid tumors. Calderasib was originated by Merck (Merck Sharp & Dohme) leveraging a structure‑based optimization strategy related to first‑generation KRAS G12C inhibitors and is being clinically evaluated as monotherapy and in combination with immune checkpoint blockade such as pembrolizumab.

Brand names

Calderasib

Other names

MK-1084MK1084MK 1084calderasib