QTX3544

QTX3544 is an oral, allosteric, multi-KRAS inhibitor with a preference for the G12V mutation. It is designed to target both the ON and OFF states of KRAS proteins, selectively preventing KRAS activation and locking the protein in an inactive conformation that is incompetent for effector signaling. This results in disruption of protein-protein interactions between various KRAS mutants and RAF1, leading to dose-dependent inhibition of MAPK signaling in multiple cancer cell lines derived from colorectal, pancreatic, ovarian, and gastric cancers carrying various KRAS mutations—especially G12V. QTX3544 has demonstrated high biochemical potency against multiple KRAS variants (with particular activity against G12V), favorable preclinical pharmacokinetics including oral bioavailability, and significant anti-tumor activity in preclinical models. The drug is currently being evaluated in a Phase 1 clinical trial enrolling patients with solid tumors harboring KRAS G12V mutations as monotherapy or combined with cetuximab.