PCS6422

PCS6422 is an investigational small molecule uracil analog that acts as an irreversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the primary enzyme responsible for the catabolism of 5-fluorouracil (5-FU). Developed by Processa Pharmaceuticals, PCS6422 is designed to be administered in combination with the oral fluoropyrimidine capecitabine in a regimen referred to as Next Generation Capecitabine (NGC-Cap). By inhibiting DPD, PCS6422 prevents the breakdown of 5-FU into toxic catabolites such as fluoro-beta-alanine (F-BAL), which are associated with dose-limiting toxicities like hand-foot syndrome and cardiotoxicity. This metabolic redirection aims to increase the exposure of cancer cells to active cytotoxic metabolites, thereby improving the therapeutic index of 5-FU-based chemotherapy. It is currently being evaluated in Phase 1b and Phase 2 clinical trials for the treatment of advanced gastrointestinal tract cancers, including colorectal and pancreatic cancers, as well as breast cancer and other solid tumors.