CHDI-00485180-R

CHDI-00485180-R is a potent, selective, and brain-penetrant small molecule inhibitor of kynurenine 3-monooxygenase (KMO). KMO is a critical enzyme in the kynurenine pathway, the primary route for tryptophan metabolism in the mammalian brain. In Huntington's disease and other neurodegenerative conditions, the kynurenine pathway is often dysregulated, leading to an overproduction of neurotoxic metabolites such as 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN), which contribute to oxidative stress and excitotoxicity. By inhibiting KMO, CHDI-00485180-R shifts the metabolic flux toward the production of kynurenic acid (KYNA), a known neuroprotective agent that acts as an antagonist at NMDA and alpha-7 nicotinic acetylcholine receptors. Developed by the CHDI Foundation, this compound serves as a valuable tool for exploring the therapeutic potential of KMO inhibition in slowing the progression of Huntington's disease.