Differential binding of Clemizole among TRPC homologs

The Transient Receptor Potential Canonical (TRPC) channels play important physiological roles and are involved in various signalling events in many organs. Amongst TRPC channels, the TRPC6 channel is one of the most studied, due to its involvement in multiple mechanisms of disease progression. Although several inhibitors of TRPC channels have been discovered, none of them have progressed to clinical trials. Clemizole is a potent TRPC5 antagonist with low affinity to TRPC6. In this study, we investigated the structural determinants and molecular aspects of TRPC5 and TRPC6 interaction with clemizole. We identified the critical clemizole binding site molecular determinants as well as the residues’ Accessible Surface Area (ASA) and Relative Accessible Surface Area (RASA) values. These results may facilitate drug discovery process.