Peer-reviewedCC BYBiochemistry
In Pursuit of Enduring Inactivation: A Perspective on the Development and Study of Irreversible-Covalent Inhibitors.
7 affiliations
- 1Department of Medicinal Chemistry, Institute for Biomedical Engineering, Faculty of Medicine, Eberhard Karls Universität Tübingen, Tübingen72076, Germany.
- 2Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Tübingen72076, Germany.
- 3Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies" Eberhard Karls Universität Tübingen, Tübingen72076, Germany.
- 4Department of Chemistry, College of Arts and Sciences, The State University of New York at Buffalo, Buffalo, New York14260, United States.
- 5Department of Structural Biology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York14203, United States.
- 6Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York14214, United States.
- 7Department of Pharmacology and Therapeutics, , Roswell Park Comprehensive Cancer Center, Buffalo, New York14203, United States.
Abstract
Molecules that form irreversible covalent bonds with their targets are a mainstay of drug discovery and chemical biology research. Their ability to permanently inactivate an enzyme target provides a mechanism with significant potential to modulate disease phenotypes. This perspective discusses the trajectory of the field of irreversible enzyme inhibitors with an outlook on emerging methods, warhead structures, and sentiments presently directing practices in the discovery and design of the next wave of covalent agents.
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BibTeX
@article{gehringer2026pursuit,
title = {{In Pursuit of Enduring Inactivation: A Perspective on the Development and Study of Irreversible-Covalent Inhibitors.}},
author = {Matthias Gehringer and David E Heppner},
journal = {Biochemistry},
year = {2026},
month = oct,
doi = {10.1021/acs.biochem.6c00624},
url = {https://europepmc.org/article/MED/42899594},
note = {CC BY},
}
RIS
TY - JOUR
TI - In Pursuit of Enduring Inactivation: A Perspective on the Development and Study of Irreversible-Covalent Inhibitors.
AU - Matthias Gehringer
AU - David E Heppner
PY - 2026
DA - 2026/10/01
JO - Biochemistry
DO - 10.1021/acs.biochem.6c00624
UR - https://europepmc.org/article/MED/42899594
AB - Molecules that form irreversible covalent bonds with their targets are a mainstay of drug discovery and chemical biology research. Their ability to permanently inactivate an enzyme target provides a mechanism with significant potential to modulate disease phenotypes. This perspective discusses the trajectory of the field of irreversible enzyme inhibitors with an outlook on emerging methods, warhead structures, and sentiments presently directing practices in the discovery and design of the next wave of covalent agents.
SN - 0006-2960
SN - 1520-4995
ER -