Cheung YY, Yu H, Xu K, Zou B, Wu M, McManus OB, Li M, Lindsley CW, Hopkins CR
J Med Chem. 2012 55 (15)
· PMCID: PMC3530927
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.
MeSH Terms (15)Animals Brain Databases, Factual High-Throughput Screening Assays Humans KCNQ2 Potassium Channel Microsomes, Liver Permeability Phenylbutyrates Potassium Channel Blockers Pyrrolidines Rats Small Molecule Libraries Stereoisomerism Structure-Activity Relationship