Identification of potent and selective MMP-13 inhibitors

A potent, selective series of MMP-13 inhibitors has been derived from a weak (3.2 μM) inhibitor that did not bear a zinc chelator. Structure-based drug design strategies were employed to append a Zn-chelating group to one end of the molecule and functionality to enhance selectivity to the other. A compound from this series demonstrated rat oral bioavailability and efficacy in a bovine articular cartilage explant model.

A potent, selective series of MMP-13 inhibitors has been derived from a weak inhibitor that did not bear a zinc chelator.Figure optionsDownload as PowerPoint slide