Transient Receptor Potential Canonical (TRPC) as a Therapeutic Drug Target

Canonical or classical transient receptor potential (TRPC) proteins are nonselective cationic channels and a subset of TRP superfamily which are ubiquitously expressed in mammalian cells. Activation of TRPC channels permits the inflow of calcium (Ca2+) and other monovalent alkali cations such as Na+ into the cytosol resulting in cell depolarization and an increase in intracellular Ca2+ concentration. Hence, TRPC channels are multifunctional signaling protein complexes that play crucial roles in a vast range of human physiological and pathological processes such as cancer, neurological disorders, cardiovascular diseases, painPain, and chronic kidney disease. Therefore, they serve as potential drug target for several human diseases and disorders. In this chapter, the TRPC structure, function, regulation, and recently identified potent and selective modulators of these channels will be discussed. Functional tetrameric TRPC channels assemble as homo- or heterotetrameric complexes. To date, seven TRPC subfamily members have been identified (TRPC1–TRPC7), and TRPC2 is a pseudogene in humans. Recent TRPC structural studies have offered new insights into channel architecture and assembly. High-resolution structures of TRPC3, TRPC4, TRPC5, and TRPC6 homotetramers have been reported. Together, potentially compound profiling will lead to discovering and characterizing novel drug candidates that are intended to generate innovative therapeutic therapies.