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Description: Adagrasib (MRTX-849) is a novel, potent, selective, orally bioavailable and covalent / irreversible inhibitor of KRAS G12C with IC50s ranging between 10 and 973 nM in the 2D format and between 0.2 and 1042 nM in the 3D format. It has potential antineoplastic activity and acts by covalently binding to KRAS G12C at the cysteine at residue 12, locking the protein in its inactive GDP-bound conformation, and inhibiting KRAS-dependent signal transduction.
References:
1. Christensen JG, et al. The KRASG12C Inhibitor, MRTX849, Provides Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers in Mouse Models and Patients. Cancer Discov. 2019 Oct 28. pii: CD-19-1167.
2. Kyriakos P. Papadopoulos, et al. A phase I/II multiple expansion cohort trial of MRTX849 in patients with advanced solid tumors with KRAS G12C mutation. Journal of Clinical Oncology 2019 37:15_suppl, TPS3161-TPS3161.
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