Current strategies for the discovery of K+ channel modulators.
Potassium ion (K(+)) channels consist of a ubiquitous family of membrane proteins that play critical roles in a wide variety of physiological processes, such as the regulation of neuronal excitability, muscle contraction, cell proliferation, and insulin secretion. Due to their pivotal functions in biological systems, K(+) channels have long been attractive targets for the rational drug design on the basis of their structures and interaction mechanisms. Various small-molecular compounds and toxins have been discovered to act as K(+) channel modulators. In the present review, we will first briefly discuss current knowledge of the structures and functions of K(+) channels, and then review the recent strategies for the discovery of K(+) channel modulators, focusing especially on the virtual screening approaches and chemical synthesis technologies.
The Center for Drug Discovery and Design, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, P. R. China.
Deju
D
Ye
Jiang
J
Wang
Kunqian
K
Yu
Yu
Y
Zhou
Hualiang
H
Jiang
Kaixian
K
Chen
Hong
H
Liu
D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D015221:Potassium Channels / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship
D026902:Potassium Channel Blockers; D015221:Potassium Channels