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Cited by 82Enzyme function and inhibitionClick Chemistry and ApplicationsCholinesterase and Neurodegenerative Diseases

Designing Irreversible Inhibitors—Worth the Effort?

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González‐Bello, Concepción·2016·ChemMedChem
DOI 10.1002/cmdc.201500469
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Abstract

Despite the unquestionable success of numerous irreversible drugs that are currently in clinical use, such as acetylsalicylic acid (Aspirin) and penicillin, the number of such approved drugs is much lower than that of noncovalent drugs. Over the years, the potential off‐target effects of these types of compounds have been the primary concern that has hampered their development. However, their remarkable advantages over noncovalent drugs and a better analysis of the risks have decreased the widespread skepticism surrounding them. The design of irreversible inhibitors is a challenge, particularly considering that in some cases their efficacy is due to complex and unexpected mechanisms of action. In this review the main advantages of irreversible inhibition are summarized, and the complexity of certain covalent modification mechanisms is highlighted with selected examples.

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Authors
González‐Bello, C.
Affiliations
Universidade de Santiago de Compostela (ES)
Corresponding author
González‐Bello, Concepción
ORCID
González‐Bello, Concepción
Venue
ChemMedChem
Publisher
Wiley
Published
2015-11-23
Volume
11
Issue
1
Pages
22-30
ISSN
  • 1860-7179 (ISSN-L)
  • 1860-7187
DOI
10.1002/cmdc.201500469
OpenAlex
W2178945265
Cited by
74
References
77
Citations by year
2026: 3 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 10 · 2018: 7 · 2017: 9 · 2016: 12
FWCI
0.94
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • ChemMedChem (publishedVersion)
  • PubMed (publishedVersion)
  • Hispana (acceptedVersion)
  • Repositorio institucional da Universidade de Santiago de Compostela (University of Santiago de Compostela) (acceptedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion)
Funders
  • Spanish Ministry of Economy and Competitiveness (SAF2013-42899-R)
  • Xunta de Galicia (GRC2013-041)
  • European Regional Development Fund (ERDF)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
  • Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
irreversible inhibitors, covalent drug design, off-target effects, aspirin, penicillin, enzyme inhibition mechanism, drug development, non-covalent inhibitors
MeSH terms
beta-Lactamases, Enzyme Inhibitors, Humans, Hydro-Lyases, Models, Molecular, Molecular Conformation, Drug Design, H(+)-K(+)-Exchanging ATPase, Small Molecule Libraries

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