JNJ-74699157

JNJ-74699157 is an orally available, small molecule inhibitor specifically designed to target the KRAS protein with a glycine-to-cysteine substitution at position 12 (KRAS G12C mutation). This mutation is commonly found in several cancers, including non-small cell lung cancer and colorectal cancer. The drug acts as a covalent inhibitor by binding irreversibly to the mutant cysteine residue of KRAS G12C, locking the protein in its inactive GDP-bound state and thereby inhibiting downstream oncogenic signaling. Developed by Janssen Research & Development (a Johnson & Johnson company), it was evaluated in phase I clinical trials for advanced solid tumors harboring the KRAS G12C mutation. However, due to dose-limiting skeletal muscle toxicities (notably increased blood creatinine phosphokinase) and lack of significant clinical benefit at tested doses, further development was discontinued[1][2][3][4][5].

Other names

KRAS G12C inhibitor JNJ-74699157