Tilt a flavin

A team from GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) and the University of Edinburgh has solved a problem that has stymied the development of kynurenine 3-monoxygenase (KMO) inhibitors -- the production of cytotoxic hydrogen peroxide -- and generated a series of compounds ripe for preclinical testing.

Last year in a Nature Medicine study led by Damian Mole, the collaborators identified KMO as a therapeutic target in mouse and rat models of acute pancreatitis, and reported results for a first-generation, oxazolidinone-based KMO inhibitor in those models (see Distillery). The team also reported results for a series of benzisoxazole-based KMO inhibitors in a Journal of Medicinal Chemistry study in March. KMO metabolizes kynurenine, which is elevated in blood of patients with severe acute pancreatitis, and the resulting metabolite causes cell damage and apoptosis...