UPF-648 is a kynurenine 3-monooxygenase (KMO) inhibitor. KMO is a key enzyme that is part of the kynurenine pathway, which is a metabolic pathway that utilizes tryptophan to produce nicotinamide adenine dinucleotide (NAD+). KMO is a potential therapeutic target for treating neurodegenerative and psychiatric disorders.
UPF-648 is a potent, active site-targeting kynurenine 3-monooxygenase (KMO; kynurenine 3-hydroxylase) inhibitor (IC50 = 20 nM) th at prevents productive binding of the substrate L-kynurenine by perturbing the local active-site structure. UPF-648 protects against neurodegeneration in a murine (30 mg/kg, i.p.) and a Drosophila (100 μM in maize media) model of Huntingtonμs disease by shifting kynurenine pathway metabolism towards enhanced neuroprotective kynurenic acid (KYNA) formation and away from the free radicals generator 3-hydroxykynurenine (3-HK) and the excitotoxic quinolinic acid (QUIN).
