Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent and Selective, Covalent Oral Inhibitor of KRASG12C.
JDQ443 is a structurally unique, covalent inhibitor of GDP-bound KRASG12C that forms novel interactions with the switch II pocket and demonstrates selective antiproliferative activity in KRAS G 12C-mutated cell lines, including those with G12C/H95 double mutations.
JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRASG12C for the Treatment of Solid Tumors.
- E. Lorthiois, M. Gerspacher, S. Cotesta
- Biology, ChemistryJournal of Medicinal Chemistry
- 18 November 2022
JDQ443 is an investigational covalent KRASG12C inhibitor derived from structure-based drug design followed by extensive optimization of two dissimilar prototypes that showed PK/PD activity in vivo and dose-dependent antitumor activity in mouse xenograft models.
Research data supporting [Unveiling the role of boroxines in metal-free carbon-carbon homologations using diazo compounds and boronic acid]
By means of computational and experimental mechanistic studies the fundamental role of boroxines in the reaction between diazo compounds and boronic acids was elucidated. Consequently, a selective…