From RAS Biochemistry to Drug Design: How Mutant Cycling & GTP Thresholds Inform Next-Generation RAS Inhibitors

  • Revisiting the core biochemistry of RAS mutants to understand how cellular GTP loading and signaling thresholds drive oncogenic transformation
  • Examining what first-generation covalent and non-covalent inhibitors revealed about mutant-specific cycling behavior and switch-II pocket accessibility
  • Applying biochemical insights from early KRAS inhibitor successes and limitations to guide the design of next-generation RAS-targeted therapies