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Updated: Aug 24, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
The design, preparation and SAR of novel small molecule sodium (Na(+)) channel blockers
Mark A Ashwell1, Jean-Marc Lapierre, Alan Kaplan
1ArQule Inc, 19 Presidential Way, Woburn, MA 01801, USA. mashwell@rqule.com
Abstract:
A parallel strategy incorporating predictive modeling of both sodium site 2 blocking activity and cytochrome p450 CYP2D6 enzyme activity as well as experimental data from ADME profiling (eADME) has been applied to the design of new small molecule sodium channel blockers. New structural motifs were identified, which combined sodium channel activity with decreased ADME liabilities. Compounds 10h (site 2, IC(50) =531 nM) and 7j (site 2, IC(50) =149 nM) were identified from two structural classes as sodium channel blockers with favorable in vitro eADME profiles.
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