BAY1128688

BAY1128688 is an orally administered, selective small molecule inhibitor of aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5). AKR1C3 is implicated in the pathology of endometriosis and other disorders by catalyzing the conversion of androstenedione to testosterone and estrone to estradiol. Inhibition of AKR1C3 reduces local estrogen and androgen production, which may help alleviate endometriosis-associated pain. The drug was developed by Bayer for the treatment of endometriosis. Clinical development included phase 1 studies in healthy women and a phase 2 trial in women with endometriosis-related pain. However, clinical trials were terminated early due to dose-dependent hepatotoxicity characterized by elevations in serum alanine transferase (ALT) after approximately 12 weeks of treatment[6][7][8]. The observed hepatotoxicity was not predicted by animal or early human studies but may be related to off-target inhibition of hepatic bile salt transporters such as OATP1B1/3[10].