Modulating the selectivity of inhibitors for prolyl oligopeptidase inhibitors and fibroblast activation protein- α for different indications

We report herein docking-guided design of a new bicyclic scaffold and synthesis of both covalent and non-covalent bicyclic inhibitors. Biological evaluation of first-of-their-kind [4.3.0] bicyclic compounds confirmed that reactive groups, or covalent warheads, are required for inhibitor activity. This work ultimately led to one scaffold yielding new POP-selective inhibitors and a dual inhibitor equipotent to the only drug targeting FAP and POP that ever reached clinical trials.PMID:35797897 | DOI:10.1016/j.ejmech.2022.114543

Source: European Journal of Medicinal Chemistry - July 7, 2022 Category: Chemistry Authors: Jessica Plescia Damien H édou Maud Eva Pousse Anne Labarre Caroline Dufresne Anthony Mittermaier Nicolas Moitessier Source Type: research