Abstract
ATP Binding Cassette (ABC) transporters form a special family of membrane proteins, characterized by homologous ATP-binding, and large, multispanning transmembrane domains. Several members of this family are primary active transporters, which significantly modulate the absorption, metabolism, cellular effectivity and toxicity of pharmacological agents. This review provides a general overview of the human ABC transporters, their expression, localization and basic mechanism of action. Then we shortly deal with the human ABC transporters as targets of therapeutic interventions in medicine, including cancer drug resistance, lipid and other metabolic disorders, and even gene therapy applications. We place a special emphasis on the three major groups of ABC transporters involved in cancer multidrug resistance (MDR). These are the classical P-glycoprotein (MDR1, ABCB1), the multidrug resistance associated proteins (MRPs, in the ABCC subfamily), and the ABCG2 protein, an ABC half-transporter. All these proteins catalyze an ATP-dependent active transport of chemically unrelated compounds, including anticancer drugs. MDR1 (Pglycoprotein) and ABCG2 preferentially extrude large hydrophobic, positively charged molecules, while the members of the MRP family can extrude both hydrophobic uncharged molecules and water-soluble anionic compounds. Based on the physiological expression and role of these transporters, we provide examples for their role in Absorption-Distribution- Metabolism-Excretion (ADME) and toxicology, and describe several basic assays which can be applied for screening drug interactions with ABC transporters in the course of drug research and development.
Keywords: ABC Transporters, homologous, P-glycoprotein, hydrophobic
Current Drug Delivery
Title: The Role of ABC Transporters in Drug Resistance, Metabolism and Toxicity
Volume: 1 Issue: 1
Author(s): Hristos Glavinas, Peter Krajcsi, Judit Cserepes and Balazs Sarkadi
Affiliation:
Keywords: ABC Transporters, homologous, P-glycoprotein, hydrophobic
Abstract: ATP Binding Cassette (ABC) transporters form a special family of membrane proteins, characterized by homologous ATP-binding, and large, multispanning transmembrane domains. Several members of this family are primary active transporters, which significantly modulate the absorption, metabolism, cellular effectivity and toxicity of pharmacological agents. This review provides a general overview of the human ABC transporters, their expression, localization and basic mechanism of action. Then we shortly deal with the human ABC transporters as targets of therapeutic interventions in medicine, including cancer drug resistance, lipid and other metabolic disorders, and even gene therapy applications. We place a special emphasis on the three major groups of ABC transporters involved in cancer multidrug resistance (MDR). These are the classical P-glycoprotein (MDR1, ABCB1), the multidrug resistance associated proteins (MRPs, in the ABCC subfamily), and the ABCG2 protein, an ABC half-transporter. All these proteins catalyze an ATP-dependent active transport of chemically unrelated compounds, including anticancer drugs. MDR1 (Pglycoprotein) and ABCG2 preferentially extrude large hydrophobic, positively charged molecules, while the members of the MRP family can extrude both hydrophobic uncharged molecules and water-soluble anionic compounds. Based on the physiological expression and role of these transporters, we provide examples for their role in Absorption-Distribution- Metabolism-Excretion (ADME) and toxicology, and describe several basic assays which can be applied for screening drug interactions with ABC transporters in the course of drug research and development.
Export Options
About this article
Cite this article as:
Glavinas Hristos, Krajcsi Peter, Cserepes Judit and Sarkadi Balazs, The Role of ABC Transporters in Drug Resistance, Metabolism and Toxicity, Current Drug Delivery 2004; 1 (1) . https://dx.doi.org/10.2174/1567201043480036
DOI https://dx.doi.org/10.2174/1567201043480036 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advancements in Robotic and AI-based Drug Discovery and Delivery for Neurological Disorders
Neurological disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, and brain tumors, pose significant challenges in drug delivery due to the blood-brain barrier's intricate structure and the complexity of neuronal networks. Traditional drug delivery methods often fall short in reaching therapeutic concentrations within the central nervous system, limiting treatment efficacy and ...read more
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...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
-
Disturbance of Inorganic Phosphate Metabolism in Diabetes Mellitus: Its Impact on the Development of Diabetic Late Complications
Current Diabetes Reviews Pancreastatin, A Regulatory Peptide that Modulates Energy Metabolism
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Design, Synthesis and Biological Evaluation of Antipicornaviral Pyrrole-Containing Peptidomimetics
Protein & Peptide Letters Immunosuppressive Properties of Mesenchymal Stem Cells: Advances and Applications
Current Molecular Medicine Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic Heart Diseases: Similarities and Differences
Current Cardiology Reviews MicroRNAs as Candidate Drug Targets for Cardiovascular Diseases
Current Drug Targets Insulin Resistance and Postprandial Hyperglycemia the Bad Companions in Natural History of Diabetes: Effects on Health of Vascular Tree
Current Diabetes Reviews Green Tea from the Far East to the Drug Store: Focus on the Beneficial Cardiovascular Effects
Current Pharmaceutical Design Chemokine Contribution in Stem Cell Engraftment into the Infarcted Myocardium
Current Stem Cell Research & Therapy How to Treat Osteoarthritis in Obese Patients?
Current Rheumatology Reviews Mitochondrial Deficits Accompany Cognitive Decline Following Single Bilateral Intracerebroventricular Streptozotocin
Current Alzheimer Research Current Treatment and Drug Discovery Against Leishmania spp. and Plasmodium spp.: A Review
Current Drug Targets Editorial(Current and Future Options for Lipid-lowering Therapy Beyond Statins)
Current Pharmaceutical Design Comparison of Salivary Antioxidants and Oxidative Stress Status in Gestational Diabetes Mellitus and Healthy Pregnant Women
Endocrine, Metabolic & Immune Disorders - Drug Targets The Evolving Roles of Nuclear Cardiology
Current Cardiology Reviews Molecular Interaction of Human Brain Acetylcholinesterase with a Natural Inhibitor Huperzine-B: An Enzoinformatics Approach
CNS & Neurological Disorders - Drug Targets Structural Basis for the Design of PPAR-γ Ligands: A Survey on Quantitative Structure- Activity Relationships
Mini-Reviews in Medicinal Chemistry Human Tissue Kallikrein: A New Bullet for the Treatment of Ischemia
Current Pharmaceutical Design Ghrelin and Metabolic Disorders
Current Protein & Peptide Science Dipeptidyl Peptidase-4 (CD26): Knowing the Function before Inhibiting the Enzyme
Current Medicinal Chemistry