Abstract
The targeting of tubulin is an important mechanism for cancer chemotherapy. However, limitations such as resistance, toxicity and incomplete tumour elimination associated with individual anti-cancer drugs have led to a need for combination therapy in cancer. It is therefore relevant to ask whether two or more drugs might be combined in a single hybrid molecule to advantageous effect. This review provides an overview of the hybrid drugs thus far investigated, in which at least one component targets tubulin. The rationale behind this approach is that the hybrid drug may have activity enhanced above and beyond that of the equivalent drug combination, or have an otherwise improved clinical outcome. Particular emphasis is placed on the investigation of activity in multidrug-resistant cancer cell lines. Attention is drawn to the difficulties encountered when developing hybrid drugs, with respect to in vivo metabolism-tracking, increased molecular bulk, and optimisation of the drug dosage ratio. The actual and potential advantages and disadvantages of such hybrid drugs when compared to single drugs or drug combinations are discussed critically and promising directions for future research is highlighted.
Keywords: Tubulin, microtubules, chemotherapy, combination therapy, resistance, hybrid, anti-cancer
Current Medicinal Chemistry
Title: Tubulin-Targeting Agents in Hybrid Drugs
Volume: 17 Issue: 7
Author(s): E. C. Breen and J. J. Walsh
Affiliation:
Keywords: Tubulin, microtubules, chemotherapy, combination therapy, resistance, hybrid, anti-cancer
Abstract: The targeting of tubulin is an important mechanism for cancer chemotherapy. However, limitations such as resistance, toxicity and incomplete tumour elimination associated with individual anti-cancer drugs have led to a need for combination therapy in cancer. It is therefore relevant to ask whether two or more drugs might be combined in a single hybrid molecule to advantageous effect. This review provides an overview of the hybrid drugs thus far investigated, in which at least one component targets tubulin. The rationale behind this approach is that the hybrid drug may have activity enhanced above and beyond that of the equivalent drug combination, or have an otherwise improved clinical outcome. Particular emphasis is placed on the investigation of activity in multidrug-resistant cancer cell lines. Attention is drawn to the difficulties encountered when developing hybrid drugs, with respect to in vivo metabolism-tracking, increased molecular bulk, and optimisation of the drug dosage ratio. The actual and potential advantages and disadvantages of such hybrid drugs when compared to single drugs or drug combinations are discussed critically and promising directions for future research is highlighted.
Export Options
About this article
Cite this article as:
Breen C. E. and Walsh J. J., Tubulin-Targeting Agents in Hybrid Drugs, Current Medicinal Chemistry 2010; 17 (7) . https://dx.doi.org/10.2174/092986710790416254
DOI https://dx.doi.org/10.2174/092986710790416254 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
TRAIL Gene Therapy: From Preclinical Development to Clinical Application
Current Gene Therapy Thematic Analysis™ : A Chemogenomic Approach to GPCR Drug Discovery
Current Topics in Medicinal Chemistry Novel Drug-Induced Pulmonary Complications in Cancer Patients You Can Save Life!
Current Respiratory Medicine Reviews Gene Therapy in Liver Diseases: State-of-the-Art and Future Perspectives
Current Gene Therapy The Genetic Landscapes of Inflammation-Driven Gastrointestinal Tract Cancers
Current Pharmaceutical Design Research Advances in Neuroblastoma Immunotherapy
Current Pediatric Reviews Peptide Receptor Radionuclide Therapy with Somatostatin Analogues in Neuroendocrine Tumors
Anti-Cancer Agents in Medicinal Chemistry Stress Related Neuroendocrine Influences in Ovarian Cancer
Current Cancer Therapy Reviews Clinical PET Imaging of Insulinoma and Beta-Cell Hyperplasia
Current Pharmaceutical Design B Cell Modulation Strategies in Autoimmunity: The SLE Example
Current Pharmaceutical Design A Comprehensive Review of Poorly Differentiated Neuroendocrine Carcinomas (pdNECs): a Niche to Find Novel Opportunities
Current Pharmaceutical Design Peptide-Receptor Ligands and Multivalent Approach
Anti-Cancer Agents in Medicinal Chemistry Comparative Studies of the Chromogranin A-Derived Neuropeptide WE-14
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Preparation of Therapeutic Dose of <sup>177</sup>Lu-DOTA-TATE Using a Novel Single Vial Freeze-dried Kit: A Comparison with ‘In-situ’ Preparation at Hospital Radiopharmacy
Current Radiopharmaceuticals PET Designated Flouride-18 Production and Chemistry
Current Topics in Medicinal Chemistry Somatostatin, Somatostatin Analogs and Somatostatin Receptor Dynamics in the Biology of Cancer Progression
Current Molecular Medicine Small Molecule Toxins Targeting Tumor Receptors
Current Pharmaceutical Design Indirect Production of No Carrier Added (NCA) <sup>177</sup>Lu from Irradiation of Enriched <sup>176</sup>Yb: Options for Ytterbium/Lutetium Separation
Current Radiopharmaceuticals Porphyrins as Radiosensitizing Agents for Solid Neoplasms
Current Pharmaceutical Design Targeting Tumors with Small Molecule Peptides
Current Cancer Drug Targets