TRPC channels are non-selective cation channels that participate in diverse physiological processes and are essential for human health.  TRPC5 is a drug target for anxiety disorder, depression and kidney disease, while inhibition of TRPC6 shows promise for the treatment of familial FSGS, a kidney disease. We present high-resolution cryo-EM structures of human TRPC5 and TRPC6 channels in complex with several distinct inhibitors. Although these small-molecule chemicals bind the channel at different sites, all of them inhibit the channels by stabilizing the pore in a closed state. These structures provide templates for further design and optimization of inhibitors targeting human TRPC channels.
 

TRPC, TRPC3, TRPC5, TRPC6, FSGS