title: Developing Molecular Pharmacology of BK Channels for Therapeutic Benefit.
abstract: High conductance, calcium-activated potassium (BK) channels (KCa1.1) are important in regulating physiologic responses in many types of tissues and, as such, present opportunities for development of new therapeutic agents. Both channel agonists and inhibitors could have therapeutic utility, depending on medical application under consideration. However, characterization of molecular pharmacology of BK channels is incomplete and has been difficult to accomplish because of paucity of chemical leads that are acceptable templates for Medicinal Chemistry investigation. Only through continued prosecution of new high-throughput screening campaigns can this situation be rectified. Examples are presented of BK channel agonist and inhibitor discovery paradigms which will be useful for progressing BK channel future drug discovery strategies.
authors.affiliation: Kanalis Consulting, L.L.C., Edison, NJ, United States. Electronic address: gkaczorowski@optonline.net.
authors.forename: G J
authors.initials: GJ
authors.lastname: Kaczorowski
authors.affiliation: Kanalis Consulting, L.L.C., Edison, NJ, United States.
authors.forename: M L
authors.initials: ML
authors.lastname: Garcia
mesh_terms: D002118:Calcium / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D049990:Membrane Transport Modulators / Q000627:therapeutic use*; D011188:Potassium / Q000378:metabolism
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D049990:Membrane Transport Modulators; D011188:Potassium; D002118:Calcium
keywords: BK agonist; BK inhibitor; Dehydrosoyasaponin I; Drug discovery; Glaucoma; Hemorrhagic shock; Iberiotoxin; Indole diterpene; Paxilline; Smooth muscle