Physiologically relevant fluorescent assay for identification of 17 β‐hydroxysteroid dehydrogenase type 10 inhibitors

This study was focused on revalidation of the most potent HSD10 inhibitors derived from benzothiazolyl urea scaffold using fluorescent-based enzymatic assay with physiologically relevant substrates of 17β-oestradiol and allopreg nanolone. The oestradiol-based assay led to the identification of two nanomolar inhibitors (IC50 70 and 346  nM) differing from HSD10 hits revealed from the formerly used assay. Both identified inhibitors were found to be effective also in allopregnanolone-based assay with non-competitive or uncompetitive mode of action. In addition, both inhibitors were confirmed to penetrate the HEK293 cells and they were able to inhibit the HSD10 enzyme in the cellular environment. Both molecules seem to be potential lead structures for further research and development of HDS10 inhibitors.

Source: Journal of Neurochemistry - July 18, 2023 Category: Neuroscience Authors: Monika Schmidt, Michaela Vaskova, Aneta Rotterova, Pavlina Fiandova, Marketa Miskerikova, Lucie Zemanova, Ondrej Benek, Kamil Musilek Tags: ORIGINAL ARTICLE Source Type: research