WhichCyp: prediction of cytochromes P450 inhibition

Spjuth, Ola; Rydberg, Patrik

doi:10.1093/bioinformatics/btt325

Cited by 59 publications

(43 citation statements)

References 20 publications

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“…CYP2C9 and CYP3A4 of ref. 54 or CYP2C9 of ref. 55) were built on severely unbalanced training sets and tested on clearly unbalanced external sets.…”

Section: One-panel-per-molecule Outputmentioning

confidence: 99%

SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

Daina

Michielin

Zoete

2017

Sci Rep

8,401

5,174

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To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.

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“…CYP2C9 and CYP3A4 of ref. 54 or CYP2C9 of ref. 55) were built on severely unbalanced training sets and tested on clearly unbalanced external sets.…”

Section: One-panel-per-molecule Outputmentioning

confidence: 99%

SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

Daina

Michielin

Zoete

2017

Sci Rep

8,401

5,174

View full text Add to dashboard Cite

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“…In contrast to scenarios that have made CDK functionality available in larger systems, a number of projects have employed the CDK as a general cheminformatics toolkit. Examples include jCompoundMapper [11], ScaffoldHunter [12, 13], OMG [14], PaDEL [15], ChemDes [16], ReactPRED [17], SMSD [18–20], WhichCyp [21], MetaPrint2D [22], MetFrag [23], and the IUPHAR/BPS Guide to Pharmacology [24], BRENDA [25] and QSAR DataBank [26] databases. A number of such tools were initially developed using older versions of the CDK and are updated to new releases as they are made available.…”

Section: Introductionmentioning

confidence: 99%

The Chemistry Development Kit (CDK) v2.0: atom typing, depiction, molecular formulas, and substructure searching

Mayfield²,

et al. 2017

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Background The Chemistry Development Kit (CDK) is a widely used open source cheminformatics toolkit, providing data structures to represent chemical concepts along with methods to manipulate such structures and perform computations on them. The library implements a wide variety of cheminformatics algorithms ranging from chemical structure canonicalization to molecular descriptor calculations and pharmacophore perception. It is used in drug discovery, metabolomics, and toxicology. Over the last 10 years, the code base has grown significantly, however, resulting in many complex interdependencies among components and poor performance of many algorithms.Results We report improvements to the CDK v2.0 since the v1.2 release series, specifically addressing the increased functional complexity and poor performance. We first summarize the addition of new functionality, such atom typing and molecular formula handling, and improvement to existing functionality that has led to significantly better performance for substructure searching, molecular fingerprints, and rendering of molecules. Second, we outline how the CDK has evolved with respect to quality control and the approaches we have adopted to ensure stability, including a code review mechanism.ConclusionsThis paper highlights our continued efforts to provide a community driven, open source cheminformatics library, and shows that such collaborative projects can thrive over extended periods of time, resulting in a high-quality and performant library. By taking advantage of community support and contributions, we show that an open source cheminformatics project can act as a peer reviewed publishing platform for scientific computing software.Graphical abstractCDK 2.0 provides new features and improved performance Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-017-0220-4) contains supplementary material, which is available to authorized users.

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“…WhichCyp, a web-based isoform specificity prediction tool, was reported as an application note by Rostkowski et al for predictions of the most likely CYP450 isoform (1A2, 2C9, 2C19, 2D6 and 3A4 isoforms) involved in the metabolism of a druglike compound. [126] This involves an implementation of SVM method along with molecular signatures built from atomic signatures to develop classification models. These atomic signatures are expressed in terms of height which is measured as the maximum number of bonds between the SOM atom and the other atoms included in the atomic signature.…”

Section: Methods For Prediction Of Cyp450 Isoform Substratesmentioning

confidence: 99%

Advances in Computational Prediction of Regioselective and Isoform-Specific Drug Metabolism Catalyzed by CYP450s.

Dixit

Deshpande

2016

ChemistrySelect

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Prediction of drug metabolism is an important step in the early lead optimization phase and preclinical studies. Its main purpose is to avoid late stage (Phase I–III) or post‐marketing withdrawals which usually results in a significant financial loss to a pharmaceutical company. Computational methods for identification of soft‐spots in the molecules (site of metabolism; SOM) and CYP450 isoforms responsible for drug metabolism have over the past ten years proved an indispensable tool towards achieving this goal. These methods can be broadly classified into i) ligand based, ii) structure based and iii) hybrid methods. In this review we discuss some of the most successful methods of SOM and isoform specificity prediction, their application domain, advantages, and limitations along with recent developments in the last 5 years in this area. Recent applications of molecular dynamics (MD), quantum mechanics (QM) and quantum mechanics/molecular mechanics (QM/MM) methodology for regioselective and isoform specific drug metabolism predictions are also discussed. Finally, a summary of these methods along with expected developments, future challenges and opportunities are discussed.

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WhichCyp: prediction of cytochromes P450 inhibition

Abstract: The WhichCyp server is freely available for use on the web at http://drug.ku.dk/whichcyp, where the WhichCyp Java program and source code is also available for download.

Cited by 59 publications

References 20 publications

SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

The Chemistry Development Kit (CDK) v2.0: atom typing, depiction, molecular formulas, and substructure searching

Advances in Computational Prediction of Regioselective and Isoform-Specific Drug Metabolism Catalyzed by CYP450s.

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