The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology
Open accessAbstract
Targeted covalent inhibitors (TCIs) are designed to bind poorly conserved amino acids by means of reactive groups, the so-called warheads. Currently, targeting noncatalytic cysteine residues with acrylamides and other α,β-unsaturated carbonyl compounds is the predominant strategy in TCI development. The recent ascent of covalent drugs has stimulated considerable efforts to characterize alternative warheads for the covalent-reversible and irreversible engagement of noncatalytic cysteine residues as well as other amino acids. This Perspective article provides an overview of warheads-beyond α,β-unsaturated amides-recently used in the design of targeted covalent ligands. Promising reactive groups that have not yet demonstrated their utility in TCI development are also highlighted. Special emphasis is placed on the discussion of reactivity and of case studies illustrating applications in medicinal chemistry and chemical biology.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Pearson, R. G. (1963) · Journal of the American Chemical Society · doi:10.1021/ja00905a001 · Cited by 10,475
DrugBank 5.0: a major update to the DrugBank database for 2018
Wishart, D. S., Feunang, Y. D., Guo, A. C., Lo, E. J., Marcu, A., Grant, J. R., Sajed, T., Johnson, D., Li, C., Sayeeda, Z., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gkx1037 · Cited by 8,404
How to improve R&D productivity: the pharmaceutical industry's grand challenge
Paul, S. M., Mytelka, D. S., Dunwiddie, C. T., Persinger, C. C., Munos, B. H., Lindborg, S. R., & Schacht, A. L. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3078 · Cited by 3,566
The molecular hallmarks of epigenetic control
Allis, C. D., & Jenuwein, T. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.59 · Cited by 2,809
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557
The resurgence of covalent drugs
Singh, J., Petter, R. C., Baillie, T. A., & Whitty, A. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3410 · Cited by 1,873
Irreversible Inhibitors of Serine, Cysteine, and Threonine Proteases
Powers, J. C., Asgian, J. L., Ekici, Ö. D., & James, K. E. (2002) · Chemical Reviews · doi:10.1021/cr010182v · Cited by 1,090
Proteome-wide covalent ligand discovery in native biological systems
Backus, K. M., Correia, B. E., Lum, K. M., Forli, S., Horning, B. D., González-Páez, G. E., Chatterjee, S., Lanning, B. R., Teijaro, J. R., Olson, A. J., et al. (2016) · Nature · doi:10.1038/nature18002 · Cited by 940
Functional and quantitative proteomics using SILAC
Mann, M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2067 · Cited by 931
Native Mass Spectrometry: What is in the Name?
Leney, A. C., & Heck, A. J. R. (2017) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-016-1545-3 · Cited by 602
Cited by
RAS-targeted therapies: is the undruggable drugged?
Moore, A. R., Rosenberg, S. C., McCormick, F., & Malek, S. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0068-6 · Cited by 1,103
Covalent inhibitors: a rational approach to drug discovery
Sutanto, F., Konstantinidou, M., & Dömling, A. (2020) · RSC Medicinal Chemistry · doi:10.1039/d0md00154f · Cited by 389
E3 Ligase Ligands for PROTACs: How They Were Found and How to Discover New Ones
Ishida, T., & Ciulli, A. (2021) · SLAS Discovery · doi:10.1177/2472555220965528 · Cited by 380
Kuljanin, M., Mitchell, D. C., Schweppe, D. K., Gikandi, A. S., Nusinow, D. P., Bulloch, N. J., Vinogradova, E. V., Wilson, D. L., Kool, E. T., Mancias, J. D., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-020-00778-3 · Cited by 305
The emerging role of mass spectrometry-based proteomics in drug discovery
Meissner, F., Geddes-McAlister, J., Mann, M., & Bantscheff, M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00409-3 · Cited by 341
Metadata
- Authors
- Gehringer, M., & Laufer, S. A.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-12-19
- Volume
- 62
- Issue
- 12
- Pages
- 5673-5724
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2904506792
- Cited by
- 714
- References
- 30
- FWCI
- 19.74
- Type
- journal article
- Language
- en
- Open access
- green
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology. https://app.cochat.ai/papers/10.1021/acs.jmedchem.8b01153
- The paper
- Gehringer, M., & Laufer, S. A. (2019). Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.8b01153
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
