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Polypharmacology in a Single Drug: Multitarget Drugs
Abstract
Polypharmacology offers a model for the way drug discovery must evolve to develop therapies most suited to treating currently incurable diseases. It is driven by a worldwide demand for safer, more effective, and affordable medicines against the most complex diseases, and by the failures of modern drug discovery to provide these. Polypharmacology can involve combinations and/or multitarget drugs (MTD). Although not mutually exclusive, my premise is that MTDs have inherent advantages over combinations. This review article focuses on MTDs from a medicinal chemistry perspective. I will explore their use in current clinical practice, their likely application in the future, and the challenges to be overcome to achieve this goal. Keywords: Multifactorial diseases, Combination therapy, multitarget drug discovery, network pharmacology, multitargetdirected ligands, designed multiple ligands
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“Both are critical issues in AD: (a) adherence to a complex therapy is unlikely for forgetful AD patients and their caregivers; (b) coexistence of chronic disease, polypharmacy, and impaired organ functions makes geriatric population particularly susceptible to DDIs.49”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [49]
In the citing paper
“Both are critical issues in AD: (a) adherence to a complex therapy is unlikely for forgetful AD patients and their caregivers; (b) coexistence of chronic disease, polypharmacy, and impaired organ functions makes geriatric population particularly susceptible to DDIs.49”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [49]
In the citing paper
“Furthermore, the single-molecule pharmacokinetic profile of hybrids, from administration to secretion, may allow to avoid DDI, that occur more frequently in AD patients, because of the coexistence of chronic disease, therapies, and impaired organ functions.49”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [49]
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Sorted by citations
A perspective on multi‐target drug discovery and design for complex diseases
Ramsay, R. R., Popović-Nikolić, M. R., Nikolic, K. M., Uliassi, E., & Bolognesi, M. L. (2018) · Clinical and Translational Medicine · doi:10.1186/s40169-017-0181-2 · Cited by 751
“In parallel, we have learned that molecules hitting more than one target may possess in principle a safer profile compared to single-targeted ones [1, 2].”
BackgroundSelf-citationPolypharmacology – Foe or Friend?
Peters, J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400856t · Cited by 485
Drug combination therapy increases successful drug repositioning
Sun, W., Sanderson, P. E. J., & Zheng, W. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.05.015 · Cited by 445
Molecular Hybridization as a Tool for Designing Multitarget Drug Candidates for Complex Diseases
Ivasiv, V., Albertini, C., Gonçalves, A. E., Rossi, M., & Bolognesi, M. L. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190619115735 · Cited by 396
Self-citationPotential Impact of the Multi-Target Drug Approach in the Treatment of Some Complex Diseases
Makhoba, X. H., Viegas, C., Mosa, R. A., Viegas, F. P. D., & Pooe, O. J. (2020) · Drug Design Development and Therapy · doi:10.2147/dddt.s257494 · Cited by 337
Metadata
- Authors
- L. Bolognesi, M.
- Venue
- Current Medicinal Chemistry
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2013-03-01
- Volume
- 20
- Issue
- 13
- Pages
- 1639-1645
- ISSN
- 0929-8673 (ISSN-L)
- OpenAlex
- W2329046360
- Cited by
- 230
- References
- 0
- Citations by year
- 2026: 15 · 2025: 7 · 2024: 23 · 2023: 11 · 2022: 27 · 2021: 23 · 2020: 35 · 2019: 19 · 2018: 12 · 2017: 16 · 2016: 13 · 2015: 13 · 2014: 9 · 2013: 7
- FWCI
- 16.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- polypharmacology, multi-target drugs, multi-target drug discovery, combination therapy, network pharmacology, multi-target-directed ligands, complex diseases
- MeSH terms
- Animals, Drug Combinations, Drug Resistance, Microbial, Pharmaceutical Preparations, Humans, Drug Discovery
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