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
-
Isolation and Characterisation of Acetylcholinesterase Inhibitors from Aquilaria subintegra for the Treatment of Alzheimer’s Disease (AD)
Current Alzheimer Research Antioxidative Properties of Flavonoids
Current Organic Chemistry Recent Trends in the Design, Synthesis and Biological Exploration of β-Lactams
Current Medicinal Chemistry Many Drugs and Phytochemicals Can Be Activated to Biological Reactive Intermediates
Current Drug Metabolism Unravelling the Role of Infectious Agents in the Pathogenesis of Human Autoimmunity: The Hypothesis of the Retroviral Involvement Revisited
Current Molecular Medicine Therapeutic Proteins: A to Z
Protein & Peptide Letters Clinical Aspects of Clara Cell 10-kDa Protein / Uteroglobin (Secretoglobin 1A1)
Current Pharmaceutical Design Privileged Structures - Dream or Reality: Preferential Organization of Azanaphthalene Scaffold
Current Medicinal Chemistry Recent Progress in the Development of Adenosine Receptor Ligands as Antiinflammatory Drugs
Current Topics in Medicinal Chemistry The Protein Profile of Fibroblasts: The Role of Proteomics
Current Proteomics A Meta-Analysis of Randomized, Placebo-Controlled Clinical Trials of Efamol® Evening Primrose Oil in Atopic Eczema. Where Do We Go from Here in Light of More Recent Discoveries?
Current Pharmaceutical Biotechnology Copper, An Ancient Remedy Returning to Fight Microbial, Fungal and Viral Infections
Current Chemical Biology Cardiovascular Magnetic Resonance for Evaluation of Heart Involvement in ANCA-Associated Vasculitis. A Luxury or a Valuable Diagnostic Tool?
Inflammation & Allergy - Drug Targets (Discontinued) Polypharmacology in Drug Discovery: A Review from Systems Pharmacology Perspective
Current Pharmaceutical Design The Use of Colchicine in Respiratory Diseases
Current Respiratory Medicine Reviews Crosstalk Between Histamine and T Cells in Allergic Diseases
Current Immunology Reviews (Discontinued) Resolution of Empyema Thoracis after Patient Refusal of Surgical Intervention: A Case Series and Review of the Literature
Current Respiratory Medicine Reviews Burner Development for the Reduction of NOx Emissions from Coal Fired Electric Utilities
Recent Patents on Mechanical Engineering Indoleamine 2,3-dioxygenase, Tregs and Cancer
Current Medicinal Chemistry Disruption of Circadian Rhythms in Critical Illness - A Role of Hyperoxia-Induced Lung Injury
Current Pharmaceutical Design