The DOI matches its Crossref record; 251 of the 251 references it cites were found in a registry or an index.
Polypharmacology by Design: A Medicinal Chemist’s Perspective on Multitargeting Compounds
Abstract
Multitargeting compounds comprising activity on more than a single biological target have gained remarkable relevance in drug discovery owing to the complexity of multifactorial diseases such as cancer, inflammation, or the metabolic syndrome. Polypharmacological drug profiles can produce additive or synergistic effects while reducing side effects and significantly contribute to the high therapeutic success of indispensable drugs such as aspirin. While their identification has long been the result of serendipity, medicinal chemistry now tends to design polypharmacology. Modern in vitro pharmacological methods and chemical probes allow a systematic search for rational target combinations and recent innovations in computational technologies, crystallography, or fragment-based design equip multitarget compound development with valuable tools. In this Perspective, we analyze the relevance of multiple ligands in drug discovery and the versatile toolbox to design polypharmacology. We conclude that despite some characteristic challenges remaining unresolved, designed polypharmacology holds enormous potential to secure future therapeutic innovation.
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“Additionally, the simultaneous modulation of multiple targets by one or more chemical entities is correlated to the concept of lower doses usage.8”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [8]
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Metadata
- Authors
- Proschak, E., Stark, H., & Merk, D.
- Affiliations
- Goethe University Frankfurt (DE)
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Merk, Daniel
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-07-23
- Volume
- 62
- Issue
- 2
- Pages
- 420-444
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2884740260
- Cited by
- 498
- References
- 251
- Citations by year
- 2026: 51 · 2025: 56 · 2024: 74 · 2023: 60 · 2022: 86 · 2021: 64 · 2020: 67 · 2019: 39 · 2018: 1
- FWCI
- 35.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Funders
- Eidgen?ssische Technische Hochschule Z?rich (16-2 FEL-07)
- Deutsche Forschungsgemeinschaft (SFB1039, PR1405/2-2, PR1405/4-1)
- European Cooperation in Science and Technology (CA15135)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Physical Sciences › Chemistry › Organic Chemistry › Heterocyclic Compound Synthesis and Bioactivity
- Keywords
- polypharmacology, multi-target drug design, drug discovery, chemical probes, fragment-based design, crystallography, computer-aided drug design, complex diseases, drug synergy, side effect reduction
- MeSH terms
- Machine Learning, Animals, Chemistry, Pharmaceutical, Humans, Ligands, Structure-Activity Relationship, Drug Design, Crystallography, X-Ray, Models, Animal, Metabolic Networks and Pathways
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