Computer-aided estimation of the hERG-mediated cardiotoxicity risk of potential drug components

Doklady. Biochemistry and Biophysics
E V RadchenkoN S Zefirov

Abstract

The hERG potassium channel is one of the most important anti-targets determining cardiotoxicity of potential drugs. Using fragmental descriptors and artificial neural networks, the predictive models of the relationship between the structure of organic compounds and their activity with respect to hERG were built, and the structural factors affecting it were analyzed. By their predictive ability and applicability domain, these models (N = 1000, Q (2) = 0.77, RMSE cv = 0.45 for affinity and N = 2886, Q (2) = 0.60, RMSE cv = 0.55 for channel inhibition) are superior to the previously published models and can be used to minimize the risk of cardiotoxicity during drug development.

References

Jun 21, 2002·SAR and QSAR in Environmental Research·I I BaskinN S Zefirov
Oct 16, 2002·Journal of Chemical Information and Computer Sciences·Nikolai S Zefirov, Vladimir A Palyulin
Mar 27, 2007·Journal of Computer-aided Molecular Design·Claire L GavaghanScott Boyer
Jul 8, 2014·European Journal of Pharmacology·Hisashi Nogawa, Tomoyuki Kawai
Aug 26, 2014·Journal of Chemical Information and Modeling·Jadel M KratzJudith M Rollinger
Apr 30, 2015·Future Medicinal Chemistry·Yankang JingIstvan J Enyedy
May 6, 2015·Doklady. Biochemistry and Biophysics·M N KuriloN S Zefirov
Feb 20, 2016·Nature Reviews. Drug Discovery·Gary GintantNorman Stockbridge
Apr 14, 2016·Scientific Reports·P SaxenaA Stary-Weinzinger

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Citations

Jul 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vladimir P BerishviliVladimir A Palyulin
Dec 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eugene V RadchenkoVladimir A Palyulin
Dec 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Galina F MakhaevaRudy J Richardson
Nov 5, 2020·International Journal of Molecular Sciences·Magdalena KowalskaAlicja Nowaczyk
Apr 9, 2021·European Journal of Medicinal Chemistry·Galina F MakhaevaRudy J Richardson
Aug 23, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Chang LiuRui Shen
Dec 28, 2021·Journal of Biomolecular Structure & Dynamics·Sudarshan LamichhaneSimon Kumar Shrestha

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