TRP Channels as Drug Targets
The superfamily of Transient Receptor Potential (TRP) channels functions as critical cellular sensors for physical and chemical changes in the intracellular and extracellular environment. There is significant interest in members of the TRP family as targets for therapeutic drug development due to the variety of physiological and pathological disease processes which they mediate.
Twenty-eight TRP homologs are present in most mammalian species. Classified in subfamilies, such as TRPA (Ankyrin), TRPV (Vanilloid), TRPC (Canonical), and TRPM (Melastatin) based on sequence homology. These membrane proteins are also distantly related to voltage-gated Na+, Ca2+, and K+ channels with similar transmembrane topology and subunit organization. TRP channels are formed of four identical or related subunits, each traversing the membrane six times, with an intervening pore loop (P-loop) between the 5th and 6th transmembrane segments. A detailed molecular picture of the structure of several of these key targets has recently emerged, which further advances drug discovery efforts.
A subset of mammalian TRP channels has received particular attention because of their roles in temperature sensing and nociception, and as such, have therapeutic potential in pain management. Three members, TRPA1, TRPV1, and TRPM8 serve as molecular detectors to produce acute and persistent pain. These thermosensitive TRP channels, or ThermoTRPs, are found on the endings of primary sensory afferent nerve fibers in the peripheral nervous system. TRPV1 and TRPA1 are co-expressed in subsets of dorsal root ganglion (DRG) neurons that innervate the skin, internal organs, the joints, as well as the eye and distributed throughout the entire human body.
Algomedix is advancing TRP research on these targets to discover new medicines that overcome limitations of existing therapeutics.