KRASG12C Inhibitor
Adagrasib (MRTX849)
Adagrasib is an investigational highly selective and potent oral small molecule therapy designed to treat some of the most complex and aggressive cancers.
Adagrasib (MRTX849)
Adagrasib is an investigational highly selective and potent oral small molecule therapy designed to treat some of the most complex and aggressive cancers.
Mechanism of Action
Mirati is developing the investigational drug candidate adagrasib, to target KRASG12C and maximize inhibition by irreversibly locking the mutant protein in its inactive state.
Preclinical studies of adagrasib demonstrated key characteristics including:
Low nanomolar potency across multiple cellular models of KRASG12C10
Only KRASG12C inhibitor with a ~ 24-hour half-life10
1,000+ fold selective for mutant KRASG12C vs wild-type KRAS and other protein cysteines10
Preclinical projection of >10-fold safety margin10
Only KRAS inhibitor where projected human volume of distribution exceeds 10L/kg10
Program Summary
Adagrasib is being explored as a monotherapy as well as in combination with other anticancer drugs. The goal is to optimize efficacy and prevent treatment resistance, ensuring these potentially promising combination therapies can help patients throughout the course of their treatment journey.
Extensive preclinical studies showed that combining adagrasib with a broad range of therapies, including PD-1, SHP2, Pan-EGFR, CDK 4/6, and SOS1 inhibitors, resulted in even more robust anti-tumor activity.
Adagrasib (MRTX849) Combination Therapy
