The DOI matches its Crossref record.
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
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
“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]
Citations
Cited by
Sorted by citations
Items 201–223 of 223
Pharmacological Characterization of Novel Histamine H4 Receptor Ligands
Nijmeijer, S. (2013) · Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam)
Integrative Systems Approaches Towards Brain Pharmacology and Polypharmacology
Bonn, R. F.-W.-U. (2013)
Networking of Smart Drugs: A Chem-Bioinformatic Approach to Cancer Treatment
Kesari, K. K., Jamal, Q. M. S., Siddiqui, M. H., & Arif, J. M. (2018) · Methods in pharmacology and toxicology · doi:10.1007/7653_2018_27 · Cited by 1
Marques, R. B. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2021.tde-06122021-121359
Bremner, J. B. (2021) · Springer eBooks · doi:10.1007/978-981-16-0999-2_1
Descubrimiento de nuevos anticonvulsivos que actúan mediante interacciones con canales iónicos
Llanos, M. A. (2022) · El Servicio de Difusión de la Creación Intelectual (National University of La Plata) · doi:10.35537/10915/140503
Silva, M. D. F., Viegas, F. P. D., Gontijo, V. S., Ortiz, C. J. C., Franco, G. D. R. R., Ernesto, J. T., Damásio, C. M., Fonseca, G. P. D. S., Silva, I. M. F., Massuda, L. E., et al. (2023) · Frontiers in clinical drug research. CNS and neurological disorders · doi:10.2174/9789815123319123110003
Jakubiec, M., Abram, M., Zagaja, M. P., Socała, K., Panic, V., Latacz, G., Mogilski, S., Szafarz, M., Szala‐Rycaj, J., Saunders, J., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4825092
Harnessing the Multitarget Approach for Green and Sustainable Drug Discovery
Vlocskó, R. B., & Török, M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15742-4.00103-4
Bioavailability and dose proportionality of a highly lipophilic phenolic antioxidant
Yanovskaya, Е. А., Фрелих, Г. А., Lakeev, A. P., et al. (2025) · Xenobiotica · doi:10.1080/00498254.2025.2465237
“Relying solely on drugs with a single pharmacological target has proven inadequate for achieving optimal treatment outcomes (Bolognesi 2013; Bolognesi and Cavalli 2016).”
Jakubiec, M., Abram, M., Zagaja, M. P., Socała, K., Panic, V., Latacz, G., Mogilski, S., Szafarz, M., Szewczyk, A., Saunders, J., et al. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118728
Tha, S., Shakya, S., Malla, R., & Aryal, P. (2020) · Figshare · doi:10.6084/m9.figshare.12246656
Tha, S., Shakya, S., Malla, R., & Aryal, P. (2020) · Figshare · doi:10.6084/m9.figshare.12246662
Tha, S., Shakya, S., Malla, R., & Aryal, P. (2020) · Figshare · doi:10.6084/m9.figshare.12246668
Tha, S., Shakya, S., Malla, R., & Aryal, P. (2020) · Figshare · doi:10.6084/m9.figshare.12246674
Repurposing of Therapeutics for Anticancer Activity
Singh, S., Mishra, N., Alka, Verma, A., Nisha, R., Singh, N., & Saraf, S. A. (2026) · Springer eBooks · doi:10.1007/978-981-95-4522-3_11
Zhao, Z.-W., Li, W.-Y., Li, W.-Z., & Wang, Y. (2026) · Journal of Chinese Integrative Medicine · doi:10.1016/j.joim.2026.02.001 · Cited by 1
Lai, X.-Y., Chang, C., & Hsu, H. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.151022
Design and in Vitro Neuroprotective Evaluation of Pyrimidine-Based Compounds for Alzheimer’s Therapy
Sharma, V., Rani, G., Rai, S., Yasmeen, A., Kumar, M., Oleti, N., Gulia, S. K., Solanki, R., & Geetha, P. (2026) · Oriental Journal Of Chemistry · doi:10.13005/ojc/420212
Ensemble and multitarget docking approaches for polypharmacology in drug discovery
Faria, & Ishrat, R. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-49253-2.00022-2
Zhou, Z., Cao, K., 姚高峰, Liu, Y., Duan, W., Yang, C., Sheng, S., & Huang, Y. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1863402
“Nevertheless, the development of multi-specific drugs poses numerous bioanalytical and methodological challenges throughout all stages of drug discovery and development (Bolognesi, 2013).”
Multi‐omics–driven precision medicine
Li, H., Zhao, Z., Zhang, Y., Ma, Y., Hu, G., Zeng, M., Yang, Z., Zhao, Z., Zhou, X., Hu, W., et al. (2026) · iMeta · doi:10.1002/imt2.70165 · Cited by 1
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
