ASN-1764

ASN-1764 (also known as ASN009) is an orally bioavailable, potent, and selective small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), an enzyme located in the inner mitochondrial membrane that catalyzes the rate-limiting step in the de novo pyrimidine biosynthesis pathway. Developed by Asana BioSciences, ASN-1764 is designed to exploit the metabolic dependency of cancer cells on de novo pyrimidine production. Inhibition of DHODH leads to the depletion of intracellular uridine monophosphate (UMP) pools, resulting in DNA replication stress, cell cycle arrest, and apoptosis. In myeloid leukemia models, ASN-1764 has demonstrated the ability to induce myeloid differentiation, providing a therapeutic rationale for its use in acute myeloid leukemia (AML). While it entered Phase 1 clinical trials for advanced solid tumors and hematologic malignancies, the development was subsequently terminated by the sponsor for strategic business reasons.