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 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Oral Beclomethasone Dipropionate: A Critical Review of its Use in the Management of Ulcerative Colitis and Crohn’s Disease
Current Clinical Pharmacology Novel Applications of Recombinant Lactic Acid Bacteria in Therapy and in Metabolic Engineering
Recent Patents on Biotechnology Innate Immunity and the Role of Epithelial Barrier During Aspergillus fumigatus Infection
Current Immunology Reviews (Discontinued) Serum Trough IgG level and Annual Intravenous Immunoglobulin Dose Are Not Related to Body Size in Patients on Regular Replacement Therapy
Drug Metabolism Letters Anti-IgE Significantly Changes Circulating Interleukin-25, Vitamin-D and Interleukin-33 Levels in Patients with Allergic Asthma
Current Pharmaceutical Design Natural Medicine:The Genus Angelica
Current Medicinal Chemistry Asthma in Adolescence: How Does this Differ from Childhood and Adult Asthma?
Current Pediatric Reviews Immunomodulatory Actions of Vitamin D Metabolites and their Potential Relevance to Human Lung Disease
Current Respiratory Medicine Reviews Subject Index To Volume 6
Current Molecular Medicine The Pollen Enigma: Modulation of the Allergic Immune Response by Non-Allergenic, Pollen-Derived Compounds
Current Pharmaceutical Design Aortic Dissection: A Review of the Pathophysiology, Management and Prospective Advances
Current Cardiology Reviews Mitochondrial Biogenesis: Regulation By Endogenous Gases During Inflammation and Organ Stress
Current Pharmaceutical Design Long-term Exposure to Cadmium in Food and Cigarette Smoke, Liver Effects and Hepatocellular Carcinoma
Current Drug Metabolism Erythropoietin Withdrawal Leads to the Destruction of Young Red Cells at the Endothelial-Macrophage Interface
Current Pharmaceutical Design Targeting Transcription: A New Concept of Anti-Inflammatory Therapy of Airway Diseases
Current Drug Targets Targeting IGF-I, IGFBPs and IGF-I Receptor System in Cancer: The Current and Future in Breast Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Drug Hypersensitivity: Epidemiology and Risk Factors
Current Pharmaceutical Design Medicinal Plants against Ischemic Stroke
Current Pharmaceutical Biotechnology The University of New Mexico Center for Molecular Discovery
Combinatorial Chemistry & High Throughput Screening The Relationship Between Cleft Lip, Maxillary Hypoplasia, Hypoxia and Phenytoin
Current Pharmaceutical Design