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A test set of 53 compounds was selected to cover a range of selective and mixed IC modulators that were tested for their effects on optically measured APD. A threshold of &gt;10% change in APD at 90% repolarization (APD<jats:sub>90<\/jats:sub>) was used to signify an effect at the top test concentration. To capture the variations observed in left ventricular midmyocardial myocyte APD data from 19 different dogs, the isAP model was calibrated to produce an ensemble of 19 model variants that could capture the shape and form of the APs and also quantitatively replicate dofetilide- and diltiazem-induced APD<jats:sub>90<\/jats:sub> changes. Provided with IC panel data only, the isAP model was then used, blinded, to predict APD<jats:sub>90<\/jats:sub> changes greater than 10%. At a simulated concentration of 30 \u03bcM and based on a criterion that six of the variants had to agree, isAP prediction was scored as showing greater than 80% predictivity of compound activity. Thus, early in drug discovery, the isAP model allows integrating separate IC data and is amenable to the throughput required for use as a virtual screen. <\/jats:p>","DOI":"10.1152\/ajpheart.00808.2011","type":"journal-article","created":{"date-parts":[[2011,12,24]],"date-time":"2011-12-24T04:51:40Z","timestamp":1324702300000},"page":"H1466-H1480","source":"Crossref","is-referenced-by-count":78,"title":["An in silico canine cardiac midmyocardial action potential duration model as a tool for early drug safety assessment"],"prefix":"10.1152","volume":"302","author":[{"given":"M. R.","family":"Davies","sequence":"first","affiliation":[{"name":"Computational Biology, Discovery Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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