Abstract
Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6-mercaptopurine (6-MP) are not effective in one-third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual differences in therapeutic response and toxicity to thiopurines are explained to a large extent by the variable formation of active metabolites, which is at least partly caused by genetic polymorphisms of the genes encoding crucial enzymes in thiopurine metabolism. In this in-depth review we discuss the genetic polymorphisms of genes encoding for glutathione S-tranferases, xanthine oxidase, thiopurine S-methyltransferase, inosine triphosphate pyrophosphatase, hypoxanthine phosphoribosyltransferase, inosine monophosphate dehydrogenase and multidrug resistance proteins. Pharmacogenetic knowledge in this field has increased dramatically and is still rapidly increasing, but the translation into practical guidelines with tailored advices will cost much effort in the near future.
Current Pharmaceutical Design
Title: Pharmacogenetics of Thiopurines in Inflammatory Bowel Disease
Volume: 16 Issue: 2
Author(s): L. J.J. Derijks and D. R. Wong
Affiliation:
Abstract: Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6-mercaptopurine (6-MP) are not effective in one-third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual differences in therapeutic response and toxicity to thiopurines are explained to a large extent by the variable formation of active metabolites, which is at least partly caused by genetic polymorphisms of the genes encoding crucial enzymes in thiopurine metabolism. In this in-depth review we discuss the genetic polymorphisms of genes encoding for glutathione S-tranferases, xanthine oxidase, thiopurine S-methyltransferase, inosine triphosphate pyrophosphatase, hypoxanthine phosphoribosyltransferase, inosine monophosphate dehydrogenase and multidrug resistance proteins. Pharmacogenetic knowledge in this field has increased dramatically and is still rapidly increasing, but the translation into practical guidelines with tailored advices will cost much effort in the near future.
Export Options
About this article
Cite this article as:
Derijks J.J. L. and Wong R. D., Pharmacogenetics of Thiopurines in Inflammatory Bowel Disease, Current Pharmaceutical Design 2010; 16 (2) . https://dx.doi.org/10.2174/138161210790112773
| DOI https://dx.doi.org/10.2174/138161210790112773 |
Print ISSN 1381-6128 |
| Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Multidisciplinary Pharmaceutical Drug Design Strategies in the Progress of Drug Discovery"
The process of developing a drug is time and money-consuming, but also fascinating. The development of numerous computational techniques, synthetic methodologies, formulation-based drug discovery, etc., has improved the drug discovery process. The process of developing new drugs is significantly hampered by drug-poor pharmacodynamics and pharmacokinetic problems. To address these challenges, ...read more
Accelerating Cancer drug discovery using Artificial intelligence and In Silico methods
The Artificial intelligence and in silico methods speed up cancer drug discovery, transforming how new treatments are developed. Artificial intelligence, along with in silico methods, allows for quick investigation of large biological datasets, helping identify potential drug targets with remarkable speed and accuracy. Machine learning models help us understand how ...read more
Advances in the Molecular Pathogenesis of Inflammatory Bowel Disease.
This thematic issue will emphasize the recent breakthroughs in the mechanisms of Inflammatory bowel disease (IBD) pathogenesis and devotes some understanding of both Crohn’s and ulcerative colitis. It is expected to include studies about cellular and genetic aspects, which help to precipitate the disease, and the immune system-gut microbiome relations ...read more
Artificial Intelligence and Computational Approaches in Drug Discovery
Computer-aided drug design (CADD) and artificial intelligence (AI) are fundamentally reshaping drug discovery pipelines by significantly enhancing efficiency in molecular screening, rational drug design, and natural product development. In the field of molecular screening, the integration of virtual high-throughput screening with advanced AI models enables rapid analysis of million-compound libraries, ...read more
- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Dasatinib: An Anti-Tumour Agent via Src Inhibition
Current Drug Targets Photodynamic Therapy: The Development of New Photosensitisers
Anti-Cancer Agents in Medicinal Chemistry Proteomics Approach to Illustrate Drug Action Mechanisms
Current Drug Discovery Technologies Targeting the BH3 Domain of Bcl-2 Family Proteins. A Brief History From Natural Products to Foldamers As Promising Cancer Therapeutic Avenues
Current Medicinal Chemistry Cardiotoxicity of Molecularly Targeted Agents
Current Cardiology Reviews Dynamics of CD86 Expression on Allergic Inflammation - New Insights
Recent Patents on Inflammation & Allergy Drug Discovery Manganese Superoxide Dismutase (Sod2) and Redox-Control of Signaling Events That Drive Metastasis
Anti-Cancer Agents in Medicinal Chemistry Pathways Related to the Anti-Cancer Effects of Metabolites Derived from Cerrado Biome Native Plants: An Update and Bioinformatics Analysis on Oral Squamous Cell Carcinoma
Protein & Peptide Letters A Novel Quinoline Based Second-generation mTOR Inhibitor that Induces Apoptosis and Disrupts PI3K-Akt-mTOR Signaling in Human Leukemia HL-60 Cells
Anti-Cancer Agents in Medicinal Chemistry Emerging Facts on Chronic Consumption of Aspartame as Food Additive
Current Nutrition & Food Science The PI3K/Akt Pathway as a Target in the Treatment of Hematologic Malignancies
Anti-Cancer Agents in Medicinal Chemistry Retinal Ganglion Cell Gene Therapy and Visual System Repair
Current Gene Therapy Effect of DNA Repair Deficiencies on the Cytotoxicity of Drugs Used in Cancer Therapy - A Review
Current Medicinal Chemistry Restoration of Chemoresistance Mechanism by Novel Drug Therapies in Breast Cancer Cell Lines
Current Drug Therapy Overview: Translating Hsp90 Biology into Hsp90 Drugs
Current Cancer Drug Targets Endoradiotherapy with Peptides - Status and Future Development
Current Medicinal Chemistry Anticancer Properties of Flavonoids: Roles in Various Stages of Carcinogenesis
Cardiovascular & Hematological Agents in Medicinal Chemistry Protective Effect of Heat Shock Proteins in the Nervous System
Current Neurovascular Research TRP Channels and Cancer: New Targets for Diagnosis and Chemotherapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Editorial (Thematic Issue: Unlocking the Potential of Stem Cells in Cell Therapy, Drug Delivery and Drug Discovery)
Current Drug Delivery





