Integrating the discovery pipeline for novel compounds targeting ion channels.
Many ion channels are attractive therapeutic targets for the treatment of neurological or cardiovascular diseases; there is a continuous need for selective channel antagonists and/or agonists. Recently, several technologies have been developed that make exploration of the enormous diversity of venom-derived peptidic toxins more feasible. Integration of exogenomics with synthetic methods such as diselenide or fluorous bridges, backbone spacers, and N-to-C cyclization provides an emerging technology that promises to accelerate discovery and development of natural products based compounds. These drug-discovery efforts are complemented by novel approaches to modulate the activities of ion channels and receptors. Taken together, these technologies will advance our knowledge and understanding of ion channels and will accelerate their expansion as targets for first-in-class therapeutics.
Bulaj
Grzegorz
G
Department of Medicinal Chemistry, College of Pharmacy, University of Utah, 421 Wakara Way, Suite 360, Salt Lake City, UT 84108, USA. bulaj@pharm.utah.edu
D000595:Amino Acid Sequence; D000818:Animals; D001682:Biological Availability; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D007473:Ion Channels / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D010084:Oxidation-Reduction; D014688:Venoms / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
D007473:Ion Channels; D009498:Neurotoxins; D014688:Venoms