CHDI-00485626

CHDI-00485626 is a potent, selective, and brain-penetrant small molecule inhibitor of kynurenine 3-monooxygenase (KMO), an enzyme that plays a critical role in the kynurenine pathway of tryptophan metabolism. Developed by the CHDI Foundation, the compound is primarily investigated for the treatment of Huntington's disease (HD). In HD, the kynurenine pathway is often imbalanced, leading to an overproduction of neurotoxic metabolites such as 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN). By inhibiting KMO, CHDI-00485626 shifts the metabolic flux toward the production of kynurenic acid (KYNA), which possesses neuroprotective properties. A distinguishing feature of CHDI-00485626 compared to earlier KMO inhibitors is its ability to cross the blood-brain barrier, enabling it to modulate the kynurenine pathway directly within the central nervous system. Preclinical studies in various mouse models of Huntington's disease have demonstrated that CHDI-00485626 can reduce neuroinflammation, improve motor deficits, and mitigate neuropathological changes.