Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule.

BMC Pharmacology
Nitish K MishraGajendra Ps Raghava

Abstract

Different isoforms of Cytochrome P450 (CYP) metabolized different types of substrates (or drugs molecule) and make them soluble during biotransformation. Therefore, fate of any drug molecule depends on how they are treated or metabolized by CYP isoform. There is a need to develop models for predicting substrate specificity of major isoforms of P450, in order to understand whether a given drug will be metabolized or not. This paper describes an in-silico method for predicting the metabolizing capability of major isoforms (e.g. CYP 3A4, 2D6, 1A2, 2C9 and 2C19). All models were trained and tested on 226 approved drug molecules. Firstly, 2392 molecular descriptors for each drug molecule were calculated using various softwares. Secondly, best 41 descriptors were selected using general and genetic algorithm. Thirdly, Support Vector Machine (SVM) based QSAR models were developed using 41 best descriptors and achieved an average accuracy of 86.02%, evaluated using fivefold cross-validation. We have also evaluated the performance of our model on an independent dataset of 146 drug molecules and achieved average accuracy 70.55%. In addition, SVM based models were developed using 26 Chemistry Development Kit (CDK) molecular descriptors and...Continue Reading

References

Mar 1, 1994·Kidney International·C A PollockC R George
Feb 7, 2001·BMJ : British Medical Journal·C R WolfR L Smith
Feb 23, 2002·Journal of Molecular Graphics & Modelling·Hua GaoJohn Van Drie
Mar 4, 2003·Nature Reviews. Drug Discovery·Han van de Waterbeemd, Eric Gifford
Mar 26, 2003·Journal of Chemical Information and Computer Sciences·Christoph SteinbeckEgon Willighagen
Jul 23, 2003·Journal of Chemical Information and Computer Sciences·Roberta G Susnow, Steven L Dixon
Dec 4, 2003·Bioorganic & Medicinal Chemistry·Shahriar Haji-MomenianMilton L Brown
Jul 3, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Konstantin V BalakinTatiana Nikolskaya
Jul 28, 2005·Journal of Chemical Information and Modeling·C W Yap, Y Z Chen
Apr 29, 2006·European Journal of Medicinal Chemistry·P Crivori, I Poggesi
Jun 27, 2006·Current Pharmaceutical Design·Christoph SteinbeckEgon L Willighagen
Aug 22, 2006·Current Topics in Medicinal Chemistry·Rieko Arimoto
Sep 22, 2006·IEEE Transactions on Pattern Analysis and Machine Intelligence·Juan J RodríguezCarlos J Alonso
Jul 5, 2007·Journal of Chemical Information and Modeling·Lothar TerflothJohann Gasteiger
Jul 14, 2007·Protein and Peptide Letters·Nitish Kumar MishraG P S Raghava
Jul 25, 2007·BMC Bioinformatics·Sneh LataG P S Raghava
Dec 1, 2007·Nucleic Acids Research·David S WishartMurtaza Hassanali
Jan 1, 1996·IEEE Transactions on Neural Networks·S V Chakravarthy, J Ghosh
Aug 7, 2008·Pharmacogenomics·David S Wishart
Mar 9, 2010·BMC Pharmacology·Deepak SinglaGajendra P S Raghava

❮ Previous
Next ❯

Citations

Apr 25, 2012·Journal of Chemical Information and Modeling·Jed ZaretzkiCurt M Breneman
Feb 22, 2013·Academic Medicine : Journal of the Association of American Medical Colleges·Benjamin KliglerNadine T Katz
Mar 25, 2011·Current Opinion in Pediatrics·Thomas Reinehr
Dec 24, 2013·Journal of Pharmacological and Toxicological Methods·Sean Ekins
Aug 26, 2011·Expert Opinion on Drug Metabolism & Toxicology·Nitish Kumar Mishra
May 11, 2015·Advanced Drug Delivery Reviews·Lars OlsenFlemming Steen Jørgensen
Jun 26, 2015·Journal of Chemical Information and Modeling·Bo-Han SuYufeng J Tseng
Apr 16, 2011·Journal of Chemical Information and Modeling·Feixiong ChengYun Tang
Apr 25, 2015·Nature Reviews. Drug Discovery·Johannes KirchmairGisbert Schneider
Jan 27, 2015·Bioinformatics·Chi-Yu ShaoYufeng J Tseng
Mar 15, 2015·Forensic Science International : Synergy·Luke N RoddaOlaf H Drummer
May 8, 2016·Journal of Interprofessional Care·Gillian NisbetJoanne Shaw
May 22, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mika NagaiKouichi Yoshinari
May 24, 2011·Journal of Chemical Information and Modeling·Sergii NovotarskyiIgor V Tetko
Apr 30, 2014·Journal of Analytical Toxicology·Luke N RoddaOlaf H Drummer
Mar 31, 2018·International Journal of Molecular Sciences·Sabina Podlewska, Rafał Kafel
Feb 22, 2018·Journal of Computer-aided Molecular Design·Peter A HuntJonathan D Tyzack
Jan 25, 2019·Current Topics in Medicinal Chemistry·Alexander V DmitrievVladimir V Poroikov
Aug 17, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kouta ToshimotoYutaka Akiyama
Sep 23, 2014·Journal of Breath Research·Susanne von GrafensteinKlaus R Liedl
Aug 1, 2020·Expert Opinion on Drug Discovery·Supratik Kar, Jerzy Leszczynski
Jul 5, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·René Escobedo-GonzálezRené Miranda-Ruvalcaba
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria PonticelliLuigi Milella
Jun 5, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yu SunJianhong Wei
Jul 12, 2019·Chemical Reviews·Xin YangShengyong Yang
Nov 27, 2018·Molecular Pharmaceutics·Lu LiuDong-Sheng Cao
Oct 17, 2021·ChemMedChem·Simone Q PantaleãoKathia Maria Honorio

❮ Previous
Next ❯

Software Mentioned

Vlife
ADMEWORKS Model Builder
SMOreg
LOOCV
BayesNet
RandomForest
CDK
light
JME
WEKA

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.