Abstract
Drug entry into cells was previously believed to be via diffusion through the lipid bilayer of the cell membrane, with the contribution to uptake by transporter proteins being of only marginal importance. Now, however, drug uptake is understood to be mainly transporter-mediated. This suggests that uptake transporters may be a major determinant of idiosyncratic drug response and a site at which drug-drug interactions occur. Accurately modelling drug pharmacokinetics is a problem of Systems Biology and requires knowledge of both the transporters with which a drug interacts and where those transporters are expressed in the body. Current physiology-based pharmacokinetic models mostly attempt to model drug disposition from the biophysical properties of the drug, drug uptake by diffusion being thereby an implicit assumption. It is clear that the incorporation of transporter proteins and their drug interactions into such models will greatly improve them. We discuss methods by which tissue localisations and transporter interactions can be determined. We propose a yeast-based transporter expression system for the initial screening of drugs for their cognate transporters. Finally, the central importance of computational modelling of transporter substrate preferences by structure-activity relationships is discussed.
Keywords: Systems Biology, drug transporter, drug uptake, pharmacokinetic modelling, Saccharomyces, cheminformatics
Current Topics in Medicinal Chemistry
Title: Implications of the Dominant Role of Transporters in Drug Uptake by Cells
Volume: 9 Issue: 2
Author(s): Paul D. Dobson, Karin Lanthaler, Stephen G. Oliver and Douglas B. Kell
Affiliation:
Keywords: Systems Biology, drug transporter, drug uptake, pharmacokinetic modelling, Saccharomyces, cheminformatics
Abstract: Drug entry into cells was previously believed to be via diffusion through the lipid bilayer of the cell membrane, with the contribution to uptake by transporter proteins being of only marginal importance. Now, however, drug uptake is understood to be mainly transporter-mediated. This suggests that uptake transporters may be a major determinant of idiosyncratic drug response and a site at which drug-drug interactions occur. Accurately modelling drug pharmacokinetics is a problem of Systems Biology and requires knowledge of both the transporters with which a drug interacts and where those transporters are expressed in the body. Current physiology-based pharmacokinetic models mostly attempt to model drug disposition from the biophysical properties of the drug, drug uptake by diffusion being thereby an implicit assumption. It is clear that the incorporation of transporter proteins and their drug interactions into such models will greatly improve them. We discuss methods by which tissue localisations and transporter interactions can be determined. We propose a yeast-based transporter expression system for the initial screening of drugs for their cognate transporters. Finally, the central importance of computational modelling of transporter substrate preferences by structure-activity relationships is discussed.
Export Options
About this article
Cite this article as:
Dobson D. Paul, Lanthaler Karin, Oliver G. Stephen and Kell B. Douglas, Implications of the Dominant Role of Transporters in Drug Uptake by Cells, Current Topics in Medicinal Chemistry 2009; 9 (2) . https://dx.doi.org/10.2174/156802609787521616
DOI https://dx.doi.org/10.2174/156802609787521616 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...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
- Announcements
Related Articles
-
A Facile and Green Synthesis of Novel Imide and Amidic Acid Derivatives of Phenacetin as Potential Analgesic and Anti-Pyretic Agents
Letters in Organic Chemistry Human Apurinic/Apyrimidinic Endonuclease (APE1): An Emerging Anti-Cancer Biomarker
Recent Patents on Biomarkers Zebrafish Model in Drug Safety Assessment
Current Pharmaceutical Design Radiolabelling of Ascorbic Acid: A New Clue to Clarify its Action as an Anticancer Agent?
Current Radiopharmaceuticals Psychiatric Side Effects of Interferon Treatment
Current Drug Safety Namitecan: a Hydrophilic Camptothecin with a Promising Preclinical Profile
Current Medicinal Chemistry A Review on the Synthesis and Anti-cancer Activity of 2-substituted Quinolines
Anti-Cancer Agents in Medicinal Chemistry Viral Based Gene Therapy for Prostate Cancer
Current Gene Therapy Patented Aptamers for C-Reactive Protein Detection: A Review About their Use in Clinical Diagnostics
Recent Patents on DNA & Gene Sequences Epigenetic Regulation of ABCB1 Transporter Expression and Function
Current Pharmacogenomics and Personalized Medicine Enzymes Metabolizing Aristolochic Acid and their Contribution to the Development of Aristolochic Acid Nephropathy and Urothelial Cancer
Current Drug Metabolism Signal Transduction Pathways of Taxanes-Induced Apoptosis
Current Medicinal Chemistry - Anti-Cancer Agents ras Genes and Human Cancer: Different Implications and Different Roles
Current Genomics Comparison of Artemisia annua Bioactivities between Traditional Medicine and Chemical Extracts
Current Bioactive Compounds Microbial Lifestyle and Genome Signatures
Current Genomics Antibody Fragment and Targeted Colorectal Cancer Therapy: A Global Systematic Review
Current Pharmaceutical Biotechnology Fundamental Concepts of the Angiogenic Process
Current Molecular Medicine Drug-Targeting Strategies for Prostate Cancer
Current Pharmaceutical Design Pharmacotherapy in Type 2 Diabetes: A Functional Schema for Drug Classification
Current Diabetes Reviews Cancer Stem Cells and their Management in Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery