1 research outputs found
Development of a Series of Kynurenine 3-Monooxygenase Inhibitors Leading to a Clinical Candidate for the Treatment of Acute Pancreatitis
Recently,
we reported a novel role for KMO in the pathogenesis
of acute pancreatitis (AP). A number of inhibitors of kynurenine 3-monooxygenase
(KMO) have previously been described as potential treatments for neurodegenerative
conditions and particularly for Huntington’s disease. However,
the inhibitors reported to date have insufficient aqueous solubility
relative to their cellular potency to be compatible with the intravenous
(iv) dosing route required in AP. We have identified and optimized
a novel series of high affinity KMO inhibitors with favorable physicochemical
properties. The leading example is exquisitely selective, has low
clearance in two species, prevents lung and kidney damage in a rat
model of acute pancreatitis, and is progressing into preclinical development