GTX-196

GTX-196 is a novel, orally available small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), currently in preclinical development by Genase Therapeutics. DHODH is a key mitochondrial enzyme involved in the de novo pyrimidine biosynthesis pathway, which is a metabolic vulnerability in cancers driven by oncogenes such as KRAS, MYC, and BRAF. By inhibiting DHODH, GTX-196 disrupts the supply of pyrimidines necessary for rapid tumor cell proliferation. Preclinical data indicates that GTX-196 maintains high potency (average IC50 of 5.1 nM) and efficacy in colorectal cancer and hematologic malignancy models. A significant advantage of this compound is its potential to avoid the systemic toxicities associated with traditional antimetabolites like 5-fluorouracil (5-FU), particularly those related to dihydropyrimidine dehydrogenase (DPD) deficiency, by selectively targeting the cancer-preferred DHODH-dependent metabolic route.