Abstract
Cytochrome P450 enzymes are the predominant mediators of phase I metabolism of exogenous small molecules. As a result of their extensive role in metabolism of xenobiotics, drug compounds, and endogenous compounds, as well as their wide tissue distribution, significant drug discovery resources are spent to avoid interacting with this class of enzymes. Here we review historical and recent in silico modeling of 7 cytochrome P450 enzymes of particular interest, specifically CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. For each we provide a brief biological background including known inhibitors, substrates, and inducers, as well as details of computational modeling efforts and advances in structural biology. We also provide similar details for 3 nuclear receptors known to regulate gene expression of these enzyme families.
Keywords: Cytochrome P450, molecular modeling, drug metabolism, Substrates, Inhibitors, Activators, Inducers, exogenous small molecules, structural biology
Combinatorial Chemistry & High Throughput Screening
Title: In Silico Modeling of P450 Substrates, Inhibitors, Activators, and Inducers
Volume: 14 Issue: 5
Author(s): Robert Kirk DeLisle, Jennifer Otten and Susan Rhodes
Affiliation:
Keywords: Cytochrome P450, molecular modeling, drug metabolism, Substrates, Inhibitors, Activators, Inducers, exogenous small molecules, structural biology
Abstract: Cytochrome P450 enzymes are the predominant mediators of phase I metabolism of exogenous small molecules. As a result of their extensive role in metabolism of xenobiotics, drug compounds, and endogenous compounds, as well as their wide tissue distribution, significant drug discovery resources are spent to avoid interacting with this class of enzymes. Here we review historical and recent in silico modeling of 7 cytochrome P450 enzymes of particular interest, specifically CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. For each we provide a brief biological background including known inhibitors, substrates, and inducers, as well as details of computational modeling efforts and advances in structural biology. We also provide similar details for 3 nuclear receptors known to regulate gene expression of these enzyme families.
Export Options
About this article
Cite this article as:
Kirk DeLisle Robert, Otten Jennifer and Rhodes Susan, In Silico Modeling of P450 Substrates, Inhibitors, Activators, and Inducers, Combinatorial Chemistry & High Throughput Screening 2011; 14 (5) . https://dx.doi.org/10.2174/138620711795508377
DOI https://dx.doi.org/10.2174/138620711795508377 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
Integrating Network Pharmacology and Traditional Medicine: A New Perspective in Drug Mechanism Research
Network pharmacology is a network construction and network topology analysis strategy that combines pharmacology and pharmacodynamics. In recent years, network pharmacology has emerged as a powerful tool that can be integrated with pharmacology. Natural products commonly function in multicomponent, multitarget, and multipathway systems. Some examples encompass Ayurveda, traditional Chinese medicines ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Role of Capecitabine in the Management of Tumors of the Digestive System
Reviews on Recent Clinical Trials Protease-Activated Receptor 2: Are Common Functions in Glial and Immune Cells Linked to Inflammation-Related CNS Disorders?
Current Drug Targets Regulatory T Cells and Allergic Disease
Inflammation & Allergy - Drug Targets (Discontinued) A Meta-Analysis of Proteomic Blood Markers of Colorectal Cancer
Current Medicinal Chemistry Meet Our Editorial Board Member:
Current Drug Targets Milk Fermented with a 15-Lipoxygenase-1-Producing Lactococcus Lactis Alleviates Symptoms of colitis in a Murine Model
Current Pharmaceutical Biotechnology Lycopene Protects Liver Against Ulcerative Colitis
Current Drug Therapy The Role of STATs in Inflammation and Inflammatory Diseases
Current Pharmaceutical Design Translating Mismatch Repair Mechanism into Cancer Care
Current Drug Targets Neoadjuvant Therapy for Resectable and Borderline Resectable Adenocarcinoma of the Pancreas
Current Drug Targets Protein Kinase C-theta Inhibitors: A Novel Therapy for Inflammatory Disorders
Current Pharmaceutical Design PPARs as Drug Targets to Modulate Inflammatory Responses?
Current Drug Targets - Inflammation & Allergy The Role and Significance of Unconventional Hydrogen Bonds in Small Molecule Recognition by Biological Receptors of Pharmaceutical Relevance
Current Pharmaceutical Design Macrophage-Assisted Inflammation and Pharmacological Regulation of the Cholinergic Anti-Inflammatory Pathway
Current Medicinal Chemistry Chemotherapy-Induced Modifications to Gastrointestinal Microflora: Evidence and Implications of Change
Current Drug Metabolism Thiopurine Immunomodulators in Ulcerative Colitis: Moving Forward with Current Evidence
Current Drug Targets Meet Our Editorial Board Member:
Current Drug Targets Radiolabelled Peptides and Monoclonal Antibodies for Therapy Decision Making in Inflammatory Diseases
Current Pharmaceutical Design Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults
Current Medicinal Chemistry Cyclooxygenase-2 Inhibitors: A Painful Lesson
Cardiovascular & Hematological Disorders-Drug Targets