Abstract
It has been widely recognised over the recent years that parallel modulation of multiple biological targets can be beneficial for treatment of diseases with complex etiologies such as cancer asthma, and psychiatric disease. In this article, current strategies for the generation of ligands with a specific multi-target profile (designed multiple ligands or DMLs) are described and a number of illustrative example are given. Designing multiple ligands is frequently a challenging endeavour for medicinal chemists, with the need to appropriately balance affinity for 2 or more targets whilst obtaining physicochemical and pharmacokinetic properties that are consistent with the administration of an oral drug. Given that the properties of DMLs are influenced to a large extent by the proteomic superfamily to which the targets belong and the lead generation strategy that is pursued, an early assessment of the feasibility of any given DML project is essential.
Keywords: Designed multiple ligands, polypharmacology, framework combination, fused and merged DMLs, hit and lead generation
Current Pharmaceutical Design
Title: Designing Multiple Ligands – Medicinal Chemistry Strategies and Challenges
Volume: 15 Issue: 6
Author(s): Richard Morphy and Zoran Rankovic
Affiliation:
Keywords: Designed multiple ligands, polypharmacology, framework combination, fused and merged DMLs, hit and lead generation
Abstract: It has been widely recognised over the recent years that parallel modulation of multiple biological targets can be beneficial for treatment of diseases with complex etiologies such as cancer asthma, and psychiatric disease. In this article, current strategies for the generation of ligands with a specific multi-target profile (designed multiple ligands or DMLs) are described and a number of illustrative example are given. Designing multiple ligands is frequently a challenging endeavour for medicinal chemists, with the need to appropriately balance affinity for 2 or more targets whilst obtaining physicochemical and pharmacokinetic properties that are consistent with the administration of an oral drug. Given that the properties of DMLs are influenced to a large extent by the proteomic superfamily to which the targets belong and the lead generation strategy that is pursued, an early assessment of the feasibility of any given DML project is essential.
Export Options
About this article
Cite this article as:
Morphy Richard and Rankovic Zoran, Designing Multiple Ligands – Medicinal Chemistry Strategies and Challenges, Current Pharmaceutical Design 2009; 15 (6) . https://dx.doi.org/10.2174/138161209787315594
DOI https://dx.doi.org/10.2174/138161209787315594 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
-
Transcriptional Regulation of Inflammatory Genes Associated with Severe Asthma
Current Pharmaceutical Design Editorial [Hot Topic: Protein Kinase Inhibitors for the Treatment of Inflammatory Disease (Guest Editor: Mark R. Player)]
Current Topics in Medicinal Chemistry MicroRNAs as Diagnostic, Prognostic and Predictive Biomarkers of Ovarian Cancer
Recent Patents on Biomarkers Benzimidazole Derivatives as Kinase Inhibitors
Current Medicinal Chemistry Keeping the Balance Between Proliferation and Differentiation:The Primary Cilium
Current Genomics HIV-1 p24-nef DNA Vaccine Plus Protein Boost Expands T-Cell Responses in BALB/c
Current Drug Delivery Polypharmacology of <i>Aconitum</i> and <i>Delphinium</i> sp. Diterpene Alka loids: Antiarrhythmic, Analgesic and Anti-Inflammatory Effects
Mini-Reviews in Organic Chemistry Cationic Surfactants and Lipids as Anti-Infective Agents
Anti-Infective Agents in Medicinal Chemistry Transforming Growth Factor-β Peptide Signaling in Lung Development: Bronchopulmonary Dysplasia, Lung Fibrosis and Emphysema
Current Respiratory Medicine Reviews Direct Covalent Modification as a Strategy to Inhibit Nuclear Factor-Kappa B
Current Medicinal Chemistry Tocilizumab in SARS-CoV-2 Patients with the Syndrome of Cytokine Storm: A Narrative Review
Reviews on Recent Clinical Trials The Relationship Between Cleft Lip, Maxillary Hypoplasia, Hypoxia and Phenytoin
Current Pharmaceutical Design Ciclesonide: A Closer Look at its Systemic and Oropharyngeal Safety Profile
Current Drug Safety Epithelial Mucus-Hypersecretion and Respiratory Disease
Current Drug Targets - Inflammation & Allergy 5-Lipoxygenase: A Promising Drug Target Against Inflammatory Diseases-Biochemical and Pharmacological Regulation
Current Drug Targets Adrenomedullin Function in Vascular Endothelial Cells: Insights from Genetic Mouse Models
Current Hypertension Reviews CRISPR/Cas9 Genome Editing Tool: A Promising Tool for Therapeutic Applications on Respiratory Diseases
Current Gene Therapy Noninvasive Assessment of Cytokines in Occupational Respiratory Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Cellular and Molecular Effects of Macrolides on Leukocyte Function
Current Pharmaceutical Design Free Radicals in Tobacco Smoke
Mini-Reviews in Organic Chemistry