Abstract
Cytochrome P450s are the most important enzymes responsible for phase I drug metabolism. The polymorphic nature of cytochrome P450s largely influences individual drug responses, drug-drug interactions and induces adverse drug reactions. By far, thirty crystal structures of eight mammalian cytochrome P450s (CYP 2C5, 2C8, 2C9, 3A4, 2D6, 2B4, 2A6 and 1A2) have been published. This review focuses on the recent studies on the structures of cytochrome P450s: some characteristic features of these enzymes and many essential, conserved amino acids in the active sites have been identified. These results are of fundamental importance for drug development and understanding the metabolism for both endogenous and xenobiotic substrates. With the help of computational methods, the structural information will provide insights into personalization of drug treatments in both proper drug therapy and appropriate dosage of a certain drug.
Keywords: Cytochrome P450, crystal structure, structure-activity relationship, polymorphism, personalized drug
Current Medicinal Chemistry
Title: Structure of Cytochrome P450s and Personalized Drug
Volume: 16 Issue: 2
Author(s): Jing-Fang Wang, Cheng-Cheng Zhang, Kuo-Chen Chou and Dong-Qing Wei
Affiliation:
Keywords: Cytochrome P450, crystal structure, structure-activity relationship, polymorphism, personalized drug
Abstract: Cytochrome P450s are the most important enzymes responsible for phase I drug metabolism. The polymorphic nature of cytochrome P450s largely influences individual drug responses, drug-drug interactions and induces adverse drug reactions. By far, thirty crystal structures of eight mammalian cytochrome P450s (CYP 2C5, 2C8, 2C9, 3A4, 2D6, 2B4, 2A6 and 1A2) have been published. This review focuses on the recent studies on the structures of cytochrome P450s: some characteristic features of these enzymes and many essential, conserved amino acids in the active sites have been identified. These results are of fundamental importance for drug development and understanding the metabolism for both endogenous and xenobiotic substrates. With the help of computational methods, the structural information will provide insights into personalization of drug treatments in both proper drug therapy and appropriate dosage of a certain drug.
Export Options
About this article
Cite this article as:
Wang Jing-Fang, Zhang Cheng-Cheng, Chou Kuo-Chen and Wei Dong-Qing, Structure of Cytochrome P450s and Personalized Drug, Current Medicinal Chemistry 2009; 16 (2) . https://dx.doi.org/10.2174/092986709787002727
DOI https://dx.doi.org/10.2174/092986709787002727 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
- Announcements
Related Articles
-
Selectivity, Binding Affinity, and Ionization State of Matrix Metalloproteinase Inhibitors
Current Pharmaceutical Design Design, Synthesis and Biological Evaluation of Palladium (II) Complexes with 1-(substituted benzyl) azetidine-3,3-dicarboxylates as Leaving Group
Medicinal Chemistry Synergism from Combination of Cisplatin and Multicentred Platinums Coded as DH6Cl and TH1 in the Human Ovarian Tumour Models
Medicinal Chemistry Synthesis and Evaluation of Anticancer Activity of 5-Ylidene-4- Aminothiazol-2(5H)-one Derivatives
Medicinal Chemistry Peripheral and Central Glutamate Dyshomeostasis in Neurodegenerative Disorders
Current Neuropharmacology Potentials of Polymeric Nanoparticle as Drug Carrier for Cancer Therapy: With a Special Reference to Pharmacokinetic Parameters
Current Drug Metabolism Novel VEGF-independent Strategies Targeting Tumor Vasculature: Clinical Aspects
Current Pharmaceutical Design Integration of Internet of Things with Quantum Dots: A State-of-the-art of Medicine
Current Pharmaceutical Design Cucurbitacin B Induces DNA Damage, G2/M Phase Arrest, and Apoptosis Mediated by Reactive Oxygen Species (ROS) in Leukemia K562 Cells
Anti-Cancer Agents in Medicinal Chemistry Structure-Based Drug Design to Overcome Drug Resistance: Challenges and Opportunities
Current Pharmaceutical Design A Brief Review of the Essential Role of Nanovehicles for Improving the Therapeutic Efficacy of Pharmacological Agents Against Tumours
Current Drug Delivery Short-term RR-Interval Power Spectral Analysis as a New Tool to Stratify the Risk of Sudden Death in Various Cardiovascular Conditions
Vascular Disease Prevention (Discontinued) “Momordica balsamina: A Medicinal and Neutraceutical Plant for Health care Management”. Comments: Biotechnological Potential of M. balsamina Revealed
Current Pharmaceutical Biotechnology STAT3 and Its Phosphorylation are Involved in HIV-1 Tat-Induced Transactivation of Glial Fibrillary Acidic Protein
Current HIV Research Disruption of Metabolic Pathways - Perspectives for the Treatment of Cancer
Current Cancer Drug Targets Targeted Delivery for Neurodegenerative Disorders Using Gene Therapy Vectors: Gene Next Therapeutic Goals
Current Gene Therapy Brain Tumor-Related Epilepsy
Current Neuropharmacology Synthesis of Aza-BODIPY Boron Difluoride PDT Agents to Promote Apoptosis in HeLa Cells
Letters in Organic Chemistry Functional Genomics- and Network-driven Systems Biology Approaches for Pharmacogenomics and Toxicogenomics
Current Drug Metabolism Liposomes: An Emerging Approach for the Treatment of Cancer
Current Pharmaceutical Design