DHODH-IN-11

DHODH-IN-11 (CAS No.: 1263303-95-2) is a synthetic small-molecule compound classified as a leflunomide-derived inhibitor of dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme that catalyzes a key step in de novo pyrimidine biosynthesis and is therefore critical for rapidly proliferating cells, including activated lymphocytes and certain cancer cells. This compound arises from structural modification of a furan-containing precursor that undergoes ring-opening transformations under physiological conditions to yield a cyano-oxime derivative, and it exhibits weak inhibitory activity against DHODH, with reduced potency potentially attributable to unfavorable stereochemical properties associated with its oxime functionality. With a pKa of approximately 5.03, DHODH-IN-11 displays physicochemical characteristics relevant to its ionization state and cellular permeability under physiological conditions. Functionally, DHODH inhibition disrupts pyrimidine nucleotide production, thereby impacting DNA and RNA synthesis and modulating cellular proliferation and immune responses. Although its inhibitory activity is comparatively modest, DHODH-IN-11 may serve as a useful chemical probe in studies aimed at elucidating structure–activity relationships within this inhibitor class or exploring the mechanistic consequences of partial DHODH blockade in biochemical assays and cell-based systems. In vitro applications typically involve low micromolar concentration ranges, with experimental dosing adjusted according to specific assay requirements and research objectives in drug discovery and pathway validation contexts.