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Designing Multiple Ligands – Medicinal Chemistry Strategies and Challenges
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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Cited by
Polypharmacology by Design: A Medicinal Chemist’s Perspective on Multitargeting Compounds
Proschak, E., Stark, H., & Merk, D. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00760 · Cited by 498
Polypharmacology – Foe or Friend?
Peters, J.-U. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400856t · Cited by 465
Modulation of P-glycoprotein efflux pump: induction and activation as a therapeutic strategy
Silva, R., Vilas-Boas, V., Carmo, H., Dinis-Oliveira, R. J., Carvalho, F., de Lourdes Bastos, M., & Remião, F. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.11.013 · Cited by 339
Guzior, N., Wi.eckowska, A., Panek, D., & Malawska, B. (2014) · Current Medicinal Chemistry · doi:10.2174/0929867321666141106122628 · Cited by 323
HIV‐1 NNRTIs: structural diversity, pharmacophore similarity, and impliations for drug design
Zhan, P., Chen, X., Li, D., Fang, Z., De Clercq, E., & Liu, X. (2013) · Medicinal Research Reviews · doi:10.1002/med.20241 · Cited by 192
Metadata
- Authors
- Morphy, R., & Rankovic, Z.
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2009-02-01
- Volume
- 15
- Issue
- 6
- Pages
- 587-600
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W1982101530
- Cited by
- 262
- References
- 0
- FWCI
- 16.42
- Type
- journal article
- Language
- en
- Open access
- closed
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