molecules of the month

Context. JDQ443 (Novartis Institute for Biomedical Research) is an oral KRASG12C inhibitor being developed for various advanced solid tumors. Despite accounting for 85% of RAS oncogenic mutations in all cancers, KRAS was considered undruggable until 2013 when a report describing the targetability of the KRASG12C mutant by small molecule inhibitors launched the oncogene back into the cancer research limelight. It is currently one of the highly pursued cancer targets, with Amgen’s KRASG12C inhibitor, the first-in-class sotorasib (Lumakras), gaining recent approval, and Mirati's NDA for adagrasib recently accepted by the FDA based on promising clinical data. Despite these advancements, emerging data on acquired resistance to adagrasib and sotorasib present a challenge that Novartis scientists believe may be overcome with JDQ443, given…