Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.1c01688
Keywords
-
Categories
Funding
- National Institute of General Medical Sciences from the National Institutes of Health [P30 GM124165]
- NIH-ORIP HEI grant [S10OD021527]
- DOE Office of Science [DE-AC02-06CH11357]
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]
- National Institutes of Health, National Institute of General Medical Sciences [P30GM133894]
- DOE Office of Biological and Environmental Research
Ask authors/readers for more resources
KRAS(G12D), the most common oncogenic KRAS mutation, is a promising target for solid tumor treatment. Selective inhibition of KRAS(G12C) presents a significant challenge due to the requirement of high affinity inhibitors to bind the mutant protein. The discovery of the noncovalent, potent, and selective KRAS(G12C) inhibitor MRTX1133, shown to be efficacious in a mouse tumor model, represents a significant advancement in the field.
KRAS(G12D), the most common oncogenic KRAS mutation, is a promising target for the treatment of solid tumors. However, when compared to KRAS(G12C), selective inhibition of KRAS(G12C) presents a significant challenge due to the requirement of inhibitors to bind KRAS(G12C) with high enough affinity to obviate the need for covalent interactions with the mutant KRAS protein. Here, we report the discovery and characterization of the first noncovalent, potent, and selective KRAS(G12C) inhibitor, inhibitor, MRTX1133, which was discovered through an extensive structure-based activity improve- ment and shown to be efficacious in a KRAS(G12C) mutant xenograft mouse tumor model.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available
Share Paper
