Fragment-Based Approaches to Enhance GTP Competitive KRAS G12C Inhibitors
Abstract
One of the cancer-causing effects of cigarette smoke is a specific genetic mutation in the KRAS gene, which results in changes in the KRAS protein at codon 12 from glycine to cysteine (G12C). KRAS G12C mutations are a major driver of cigarette smoke-associated lung cancers,occurring in ~23,000 new cases of lung cancer per year. The Westover lab and collaborators previously developed small molecule inhibitors such as SML-8-73-1 that, in a test tube, irreversibly attach to cysteine 12 and inactivate KRAS G12C protein; however, these molecules have poor pharmacological properties. The overall goal of the current project is to improve on these results by developing KRAS G12C inhibitors with pharmacological properties that would allow advancement into preclinical animal models and clinical studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1095449
Entities
People
- Kenneth D Westover
Organizations
- University of Texas Southwestern Medical Center