molecules of the month

Gout is caused by the buildup of uric acid. The main treatments are drugs that increase uric acid secretion (uricosurics, e.g. probenecid) and xanthine oxidase inhibitors which inhibit uric acid production (e.g. allopurinol). URAT1 inhibitors like lesinurad (Ironwood Pharmaceuticals) and dotinurad are emerging treatments, inhibiting uric acid reuptake.  Ironwood discontinued lesinurad for commercial reasons (which carried a black box warning at approval for acute renal failure) in 2019. Pfizer observed acute kidney injury in a Ph. I trial with a URAT1/xanthine oxidase dual inhibitor (PF-06743649). This may not be a class effect, however, as dotinurad (approved in Japan) appears to be well-tolerated. HR011303 was published in 2016 by Hengrui, and was identified by a pharmacophore-based approach to guide the lead…