BI-3231, an enzymatic inhibitor of HSD17B13, reduces lipotoxic effects induced by palmitic acid in murine and human hepatocytes
Lucía Alcober-Boquet, Nico Kraus, Lisa Sophie Huber, Rajkumar Vutukuri, Dominik C. Fuhrmann, Claudia Stroß, Liliana Schaefer, Klaus Scholich, Stefan Zeuzem, Albrecht Piiper, Marcel H. Schulz, Jonel Trebicka, Christoph Welsch, Cristina Ortiz
Abstract
17-β-Hydroxysteroid dehydrogenase 13 (HSD17B13) is a lipid droplet protein primarily expressed in the liver hepatocytes. HSD17B13 is associated with the clinical outcome of chronic liver diseases and is therefore a target for the development of drugs. Here, we demonstrate the promising therapeutic effect of BI-3231 as a potent inhibitor of HSD17B13 based on its ability to inhibit triglyceride accumulation in lipid droplets (LDs), restore lipid metabolism and homeostasis, and increase mitochondrial activity in vitro.