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http://dx.doi.org/10.17480/psk.2015.59.4.151

Novel Lead Optimization Strategy Using Quantitative Structure-Activity Relationship and Physiologically-Based Pharmacokinetics Modeling  

Byeon, Jin-Ju (College of Pharmacy, Chungnam National University)
Park, Min-Ho (College of Pharmacy, Chungnam National University)
Shin, Seok-Ho (College of Pharmacy, Chungnam National University)
Shin, Young Geun (College of Pharmacy, Chungnam National University)
Publication Information
YAKHAK HOEJI / v.59, no.4, 2015 , pp. 151-157 More about this Journal
Abstract
The purpose of this study is to demonstrate how lead compounds are best optimized with the application of in silico QSAR and PBPK modeling at the early drug discovery stage. Several predictive QSAR models such as $IC_{50}$ potency model, intrinsic clearance model and brain penetration model were built and applied to a set of virtually synthesized library of the BACE1 inhibitors. Selected candidate compounds were also applied to the PBPK modeling for comparison between the predicted animal pharmacokinetic parameters and the observed ones in vivo. This novel lead optimization strategy using QSAR and PBPK modelings could be helpful to expedite the drug discovery process.
Keywords
lead optimization; QSAR modeling; PBPK modeling; $StarDrop^{TM}$; ADMET $predictor^{TM}$; $GastroPlus^{TM}$;
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