The DOI matches its Crossref record; 330 of the 330 references it cites were found in a registry or an index.
Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions
Open accessAbstract
Although Michael acceptors display a potent and broad spectrum of bioactivity, they have largely been ignored in drug discovery because of their presumed indiscriminate reactivity. As such, a dearth of information exists relevant to the thiol reactivity of natural products and their analogues possessing this moiety. In the midst of recently approved acrylamide-containing drugs, it is clear that a good understanding of the hetero-Michael addition reaction and the relative reactivities of biological thiols with Michael acceptors under physiological conditions is needed for the design and use of these compounds as biological tools and potential therapeutics. This Perspective provides information that will contribute to this understanding, such as kinetics of thiol addition reactions, bioactivities, as well as steric and electronic factors that influence the electrophilicity and reversibility of Michael acceptors. This Perspective is focused on α,β-unsaturated carbonyls given their preponderance in bioactive natural products.
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.
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
“Preliminary clinical studies have shown that osimertinib is capable of inhibiting the L858R mutant of EGFR up to 12 nM, and the IC50 of L858R/T790M mutant was 1 nM.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [132]
In the citing paper
“The inhibition rate of osimertinib against EGFRL858R/T790M mutant was approximately 200-fold higher than that of the wild type.132”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [132]
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
Absolute hardness: companion parameter to absolute electronegativity
Parr, R. G., & Pearson, R. G. (1983) · Journal of the American Chemical Society · doi:10.1021/ja00364a005 · Cited by 7,998
Parr, R. G., von Szentpály, L., & Liu, S. (1999) · Journal of the American Chemical Society · doi:10.1021/ja983494x · Cited by 7,564
Baell, J. B., & Holloway, G. A. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm901137j · Cited by 4,196
Therapeutic potential of resveratrol: the in vivo evidence
Baur, J. A., & Sinclair, D. A. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2060 · Cited by 3,958
Density functional approach to the frontier-electron theory of chemical reactivity
Parr, R. G., & Yang, W. (1984) · Journal of the American Chemical Society · doi:10.1021/ja00326a036 · Cited by 3,672
Hard and soft acids and bases, HSAB, part 1: Fundamental principles
Pearson, R. G. (1968) · Journal of Chemical Education · doi:10.1021/ed045p581 · Cited by 2,566
Cross, D. A. E., Ashton, S. E., Ghiorghiu, S., Eberlein, C., Nebhan, C. A., Spitzler, P. J., Orme, J. P., Finlay, M. R. V., Ward, R. A., Mellor, M. J., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0337 · Cited by 2,246
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
Prodrugs: design and clinical applications
Rautio, J., Kumpulainen, H., Heimbach, T., Oliyai, R., Oh, D.-M., Järvinen, T., & Savolainen, J. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2468 · Cited by 1,681
Research works printed but not linked: 6
- Parsons Z. D., 2013, Methods in Enzymology Vol. 528: Hydrogen Peroxide and Cell Signaling Part C, 528, 130
- 2014, FDA Approves Imbruvica to Treat Chronic Lymphocytic Leukemia
- gNodwell, M. B.; Sieber, S. A.Activity-Based Protein Profiling.Springer-Verlag:Berlin, 2012; Vol.324, p165;
- Atsmon J., 1990, Cancer Res., 50, 1879
- Cavalieri E., 2004, Methods in Enzymology, 382, 293
- Geroni C., 2002, Cancer Res., 62, 2332
Cited by
Sorted by citations
The Clinical KRAS(G12C) Inhibitor AMG 510 Drives Anti-Tumour Immunity
Canon, J., Rex, K., Saiki, A. Y., Mohr, C., Cooke, K., Bagal, D., Gaida, K., Holt, T., Knutson, C. G., Koppada, N., et al. (2019) · Nature · doi:10.1038/s41586-019-1694-1 · Cited by 2,277
Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects
Kotha, R. R., & Luthria, D. L. (2019) · Molecules · doi:10.3390/molecules24162930 · Cited by 960
The SARS-CoV-2 main protease as drug target
Ullrich, S., & Nitsche, C. (2020) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2020.127377 · Cited by 787
Gehringer, M., & Laufer, S. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01153 · Cited by 772
Put a ring on it: application of small aliphatic rings in medicinal chemistry
Bauer, M. R., Fruscia, P. D., Lucas, S. C. C., Michaelides, I. N., Nelson, J. E., Storer, R. I., & Whitehurst, B. C. (2021) · RSC Medicinal Chemistry · doi:10.1039/d0md00370k · Cited by 505
Metadata
- Authors
- Jackson, P. A., Widen, J. C., Harki, D. A., & Brummond, K. M.
- Affiliations
- University of Pittsburgh (US)
- University of Minnesota (US)
- Corresponding author
- Harki, Daniel A.
- Brummond, Kay M.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-12-20
- Volume
- 60
- Issue
- 3
- Pages
- 839-885
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- PMC
- PMC5308545
- OpenAlex
- W2564708666
- Cited by
- 588
- References
- 329
- Citations by year
- 2026: 88 · 2025: 71 · 2024: 80 · 2023: 51 · 2022: 58 · 2021: 74 · 2020: 72 · 2019: 51 · 2018: 27 · 2017: 15
- FWCI
- 14.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01-GM054161, R01-GM110129)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Physical Organic Chemistry and Reaction Kinetics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and Reactivity of Sulfur-Containing Compounds
- Keywords
- α,β-unsaturated carbonyl compounds, Michael acceptors, hetero-Michael addition, thiol reactivity, acrylamide, electrophilicity, reaction kinetics, steric and electronic effects, natural products, drug design, biological activity
- MeSH terms
- Humans, Ketones, Sulfhydryl Compounds, Drug Design, Cell Line, Tumor, ErbB Receptors
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
