UCP1162

UCP1162 is a novel, non-classical antifolate small molecule designed to inhibit dihydrofolate reductase (DHFR). Unlike classical antifolates such as methotrexate, UCP1162 is engineered to bypass common resistance mechanisms; it does not appear to require the reduced folate carrier (RFC) for cellular entry or folylpolyglutamate synthase (FPGS) for intracellular activation. In preclinical studies, UCP1162 has demonstrated significantly higher potency (lower EC50) compared to methotrexate across various cancer cell lines, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and colorectal cancer. Its mechanism of action involves the depletion of deoxyribonucleotide triphosphate (dNTP) pools, which inhibits DNA synthesis and leads to cell cycle arrest in the S-phase.