Using Cheminformatics in Drug Discovery

Handbook of Experimental Pharmacology
Michael S LawlessRobert D Clark

Abstract

This chapter illustrates how cheminformatics can be applied to designing novel compounds that are active at the primary target and have good predicted ADMET properties. Examples of various cheminformatics techniques are illustrated in the process of designing inhibitors that inhibit both cyclooxygenase isoforms but are more potent toward COX-2. The first step in the process is to create a knowledge database of cyclooxygenase inhibitors in the public domain. This data was analyzed to find activity cliffs - small structural changes that result in drastic changes in potency. Additional cyclooxygenase potency and selectivity trends were obtained using matched molecular pair analysis. QSAR models were then developed to predict cyclooxygenase potency and selectivity. Next, computational algorithms were used to generate novel scaffolds starting from known cyclooxygenase inhibitors. Nine virtual libraries containing 240 compounds each were constructed. Predictions from the cyclooxygenase QSAR models were used to eliminate molecules with undesirable potency or selectivity. Additionally, the compounds were screened in silico for undesirable ADMET properties, e.g., low solubility, permeability, metabolic stability, or high toxicity, using...Continue Reading

Citations

Sep 12, 2017·Advanced Healthcare Materials·Cecilia SahlgrenNiklas Sandler
May 16, 2018·Pest Management Science·Robert D Clark
Jul 13, 2018·Expert Opinion on Drug Discovery·George Lambrinidis, Anna Tsantili-Kakoulidou
Nov 17, 2016·F1000Research·Rajan SharmaSteven M Muskal
Jul 19, 2016·F1000Research·Rajan SharmaSteven M Muskal
Jul 19, 2016·F1000Research·Rajan SharmaSteven M Muskal
Dec 24, 2020·Expert Opinion on Drug Discovery·George Lambrinidis, Anna Tsantili-Kakoulidou
Nov 10, 2018·Journal of Chemical Information and Modeling·Noé SturmHongming Chen
Dec 28, 2016·Journal of Chemical Information and Modeling·Naman PaulArtem Cherkasov

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