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.
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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 |
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