PHT-782

PHT-782 is a small molecule inhibitor of the pleckstrin homology (PH) domain of CNKSR1 (connector enhancer of kinase suppressor of RAS 1). CNKSR1 is a scaffold protein that facilitates the formation of KRAS signaling nanoclusters at the plasma membrane. By binding to the PH domain of CNKSR1, PHT-782 prevents the protein's association with membrane phosphatidylinositols, thereby disrupting mutant KRAS signaling and inhibiting the growth of KRAS-mutant cancer cells, such as non-small cell lung cancer (NSCLC) and pancreatic cancer. Notably, PHT-782 demonstrates selectivity for mutant KRAS over wild-type KRAS. It was developed by PHusis Therapeutics using in-silico docking and the PHuDock® platform.