Abstract
The clinical treatment of multifactorial pathologies (e.g. cancer, Alzheimer’s disease, psychiatric disorders), is still a major challenge. Many researches have been published dealing with the design of multiple ligands, able to act at the same time towards several targets relevant for a given pathology. In the present review, the clinical results about these compounds have been reported, together with the design strategy adopted, in order to allow a critical evaluation of the outcomes of these efforts. What is emerging is that several effective design strategies of multitarget compounds are available, and the choice among these appears to be dependent on the therapeutic area considered. However, at present, besides multitarget drugs discovered during optimization efforts by means of phenotypic assays, drug coadministrations or fixed dose formulations appear to be more useful therapeutic options than designed multiple ligands; this scenario will change when systems biology will be able to select critical targets, i.e. nodal proteins that should be inhibited in order to obtain a therapeutic action; at this point, the design of multiple ligands will allow a renaissance of medicinal chemistry.
Keywords: Design strategy, drug coadministration, multifactorial pathologies, designed multiple ligands, multitarget compounds, polypharmacology, neurodegenerative syndromes treatment, psychiatric disorders treatment, cardiovascular diseases treatment, diabetes treatment, cancer treatment, anti-inflammatory compounds, antihistamines, antibacterials, antiparasitic
Current Medicinal Chemistry
Title:Designed Multiple Ligands: Basic Research vs Clinical Outcomes
Volume: 19 Issue: 20
Author(s): L. Costantino and D. Barlocco
Affiliation:
Keywords: Design strategy, drug coadministration, multifactorial pathologies, designed multiple ligands, multitarget compounds, polypharmacology, neurodegenerative syndromes treatment, psychiatric disorders treatment, cardiovascular diseases treatment, diabetes treatment, cancer treatment, anti-inflammatory compounds, antihistamines, antibacterials, antiparasitic
Abstract: The clinical treatment of multifactorial pathologies (e.g. cancer, Alzheimer’s disease, psychiatric disorders), is still a major challenge. Many researches have been published dealing with the design of multiple ligands, able to act at the same time towards several targets relevant for a given pathology. In the present review, the clinical results about these compounds have been reported, together with the design strategy adopted, in order to allow a critical evaluation of the outcomes of these efforts. What is emerging is that several effective design strategies of multitarget compounds are available, and the choice among these appears to be dependent on the therapeutic area considered. However, at present, besides multitarget drugs discovered during optimization efforts by means of phenotypic assays, drug coadministrations or fixed dose formulations appear to be more useful therapeutic options than designed multiple ligands; this scenario will change when systems biology will be able to select critical targets, i.e. nodal proteins that should be inhibited in order to obtain a therapeutic action; at this point, the design of multiple ligands will allow a renaissance of medicinal chemistry.
Export Options
About this article
Cite this article as:
Costantino L. and Barlocco D., Designed Multiple Ligands: Basic Research vs Clinical Outcomes, Current Medicinal Chemistry 2012; 19 (20) . https://dx.doi.org/10.2174/092986712801215883
DOI https://dx.doi.org/10.2174/092986712801215883 |
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
-
Bridging the Gap Between Chemistry and Biotechnology - Large Molecules with Potential, How Could Biotechnology Complement Chemistry?
Current Organic Chemistry Aliskiren: A Novel Renin Inhibitor for Hypertension
Current Drug Therapy Renin-Angiotensin System in Diabetes
Protein & Peptide Letters Prediction by Pharmacogenetics of Safety and Efficacy of Non-Steroidal Anti- Inflammatory Drugs: A Review
Current Drug Metabolism Therapeutic Progress and Knowledge Basis on the Natriuretic Peptide System in Heart Failure
Current Topics in Medicinal Chemistry Clinical Experience with the Use of Angiotensin Receptor Blockers in Patients with Cardiovascular, Cerebrovascular and Renal Diseases
Current Clinical Pharmacology Thrombolytic Therapy in Acute Ischemic Stroke - Basic Concepts
Current Vascular Pharmacology Hypertension in Older Patients
Current Hypertension Reviews Review on Plants with Traditional Uses and Bio-activity against Hair Graying
Current Traditional Medicine Adverse Effects of Antihistamines on Skin Tests and Antihistamines in Pregnancy
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Cow’s Milk Allergy in Children, from Avoidance to Tolerance
Endocrine, Metabolic & Immune Disorders - Drug Targets The Dietary Paradox in Food Allergy: Yesterday's Mistakes, Today's Evidence and Lessons for Tomorrow
Current Pharmaceutical Design Antihistamine Use in Dermatologic Disorders
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Advances in Inhibitors of FXa
Current Drug Targets Editorial (Hot Topic: Inflammation, Coagulation, Vascular Permeability and Thrombosis)
Current Vascular Pharmacology Adverse Effects and Drug Interactions of Biologic Agents
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Action Mechanism of Antihistamines and the New Antihistamines
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Pharmacogenomics of Asthma
Current Pharmaceutical Design Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery The Challenges of Blood Pressure Control in Dialysis Patients
Recent Advances in Cardiovascular Drug Discovery (Discontinued)