molecules of the month

dotinurad (FYU-981) potently inhibits uric acid uptake by renal proximal tubule epithelial cells, increasing uric acid urinary secretion which can help hyperuricemic conditions like gout. The mechanism of action is believed to be inhibition of the URAT1 organic anion transporter which mediates uric acid reabsorption. Benzbromarone has been used for a long time in many countries to increase uric acid secretion, but is associated with rare but severe hepatic toxicities that are suspected to involve mitochondrial inhibitory activity. The authors therefore made mitigation of DILI risk a priority for this program and were successful in identifying a potent compound with low mitochondrial inhibitory activity.