Channelpedia

PubMed 22793372


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , Kv7.2



Title: Discovery of a series of 2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)acetamides as novel molecular switches that modulate modes of K(v)7.2 (KCNQ2) channel pharmacology: identification of (S)-2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)butanamide (ML252) as a potent,

Authors: Yiu-Yin Cheung, Haibo Yu, Kaiping Xu, Beiyan Zou, Meng Wu, Owen B McManus, Min Li, Craig W Lindsley, Corey R Hopkins

Journal, date & volume: J. Med. Chem., 2012 Aug 9 , 55, 6975-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22793372


Abstract
A potent and selective inhibitor of KCNQ2, (S)-5 (ML252, IC(50) = 69 nM), was discovered after a high-throughput screen of the MLPCN library was performed. SAR studies revealed a small structural change (ethyl group to hydrogen) caused a functional shift from antagonist to agonist activity (37, EC(50) = 170 nM), suggesting an interaction at a critical site for controlling gating of KCNQ2 channels.