DHODH-IN16-ADC

DHODH-IN16-ADC is a first-in-class antibody-drug conjugate (ADC) designed to selectively deliver a potent dihydroorotate dehydrogenase (DHODH) inhibitor, DHODH-IN16, to cancer cells, specifically targeting acute myeloid leukemia (AML). Unlike traditional cytotoxic ADCs, this agent acts as an immune-boosting therapeutic by disrupting mitochondrial redox balance and electron transport chain (ETC) dynamics. Inhibition of DHODH reroutes metabolic flux toward ETC Complex I, leading to Complex I hyperactivation, mitochondrial DNA (mtDNA) instability, and leakage of mtDNA into the cytosol. This cytosolic mtDNA activates the cGAS-STING pathway, inducing a robust Type I interferon (IFN-I) response that converts "immune-cold" tumors into "immune-hot" environments. This mechanism sensitizes OXPHOS-dependent cancers to immunotherapies such as immune checkpoint inhibitors and CAR-T cell therapy while sparing systemic immune cells from the immunosuppressive effects typically associated with systemic DHODH inhibition.

Other names

dihydroorotate dehydrogenase inhibitor antibody-drug conjugateDHODH-IN16 ADCDHODH-IN-16 ADCDHODH-IN 16 ADC