Precision Pipeline
FMC-376:
Drugging both the active and inactive forms of KRAS G12C
Frontier’s lead program, FMC-376, directly targets both the ON+OFF forms of KRAS G12C with exquisite selectivity. This differentiated mechanism of action offers the potential to overcome the resistance and lack of response seen with current KRAS G12C single-acting treatments.
Mechanism of Action
Watch the video to learn how the dual inhibitor FMC-376 targets both the active and inactive form of KRAS G12C.
Activated KRAS G12C
The KRAS protein is a small membrane-bound GTPase important for multiple cancer cell-signaling functions. It exists in two states. When bound to GDP, it is “OFF,” or inactive. When GDP is exchanged for GTP (usually in response to various growth stimuli), KRAS is activated, or turned “ON,” activating downstream signaling to promote cell proliferation and survival. KRAS returns to the inactive “OFF” state when GTP is hydrolyzed to GDP. Cancers can arise when KRAS signaling gets stuck in the active “ON” state. Activation occurs through multiple mechanisms, most often through activating mutations of KRAS. Mutations activate KRAS by shifting the balance towards a GTP-loaded or active “ON” state, triggering tumor proliferation and survival.