Design and application of synthetic 17B-HSD13 substrates reveals preserved catalytic activity of protective human variants.

ABSTRACT: Several hydroxysteroid dehydrogenase 17-beta 13 variants have previously been identified as protective against metabolic dysfunction-associated steatohepatitis (MASH) fibrosis, ballooning and inflammation, and as such this target holds significant therapeutic potential. However, over 5 years later, the function of 17B-HSD13 remains unknown. Structure-aided design enables the development of potent and selective sulfonamide-based 17B-HSD13 inhibitors. In order to probe their inhibitory potency in endogenous expression systems like primary human hepatocytes, inhibitors are transformed into synthetic surrogate substrates with distinct selectivity advantages over substrates previously published. Their application to cells endogenously expressing 17B-HSD13 enables quantitative measures of enzyma

SUBMITTER: Garnsey MR 

PROVIDER: S-EPMC11697577 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature