The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Proteome-wide covalent ligand discovery in native biological systems
Open accessAbstract
Small molecules are powerful tools for investigating protein function and can serve as leads for new therapeutics. Most human proteins, however, lack small-molecule ligands, and entire protein classes are considered 'undruggable'. Fragment-based ligand discovery can identify small-molecule probes for proteins that have proven difficult to target using high-throughput screening of complex compound libraries. Although reversibly binding ligands are commonly pursued, covalent fragments provide an alternative route to small-molecule probes, including those that can access regions of proteins that are difficult to target through binding affinity alone. Here we report a quantitative analysis of cysteine-reactive small-molecule fragments screened against thousands of proteins in human proteomes and cells. Covalent ligands were identified for >700 cysteines found in both druggable proteins and proteins deficient in chemical probes, including transcription factors, adaptor/scaffolding proteins, and uncharacterized proteins. Among the atypical ligand-protein interactions discovered were compounds that react preferentially with pro- (inactive) caspases. We used these ligands to distinguish extrinsic apoptosis pathways in human cell lines versus primary human T cells, showing that the former is largely mediated by caspase-8 while the latter depends on both caspase-8 and -10. Fragment-based covalent ligand discovery provides a greatly expanded portrait of the ligandable proteome and furnishes compounds that can illuminate protein functions in native biological systems.
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
“Although human CASP10 shares some degree of substrate specificity with CASP8 [317] and possibly contributes to extrinsic apoptosis in primary T cells [318]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [318]
In the citing paper
“Covalent inhibitors have been reported to achieve high efficiency through forming covalent bonds with cysteine or other nucleophilic residues in the target protein.”
From The design and development of covalent protein-protein interaction inhibitors for cancer treatment (2020) · cites this paper as [53]
In the citing paper
“Reactive cysteine residues on proteins have high nucleophilicity, which enables covalent binding with electrophilic small molecules [53, 54].”
From The design and development of covalent protein-protein interaction inhibitors for cancer treatment (2020) · cites this paper as [53]
In the citing paper
“In this study, more than 700 ligandable cysteines were identified, and information was provided about the proteome-wide selectivity of each covalent fragment in the library.”
From Advances in covalent drug discovery (2022) · cites this paper as [180]
In the citing paper
“The use of competitive isoTOP-ABPP was expanded to identify proteome-wide targets of a small covalent fragment library by competing individual acrylamide and chloroacetamide fragments against an iodoacetamide–alkyne probe180.”
From Advances in covalent drug discovery (2022) · cites this paper as [180]
In the citing paper
“showing that this approach can rapidly identify compounds that target proteins of biological interest.”
From Advances in covalent drug discovery (2022) · cites this paper as [180]
In the citing paper
“The covalent ligands discovered with this approach and their corresponding ligandable sites were used to help elucidate the role of caspase 8 and caspase 10 in extrinsic apoptosis in T cells”
From Advances in covalent drug discovery (2022) · cites this paper as [180]
In the citing paper
“We finally observed limited overlap of enantioprobe targets with proteins that demonstrated ligandability in previous chemical proteomic studies using cysteine-26,27 or lysine-reactive28 electrophilic fragments (Fig. 3b)”
From Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs (2019) · cites this paper as [26]
In the citing paper
“prior to further processing using a well-validated method for covalent ligand target identification—isotopic tandem orthogonal proteolysis ABPP (isoTOP-ABPP) 2,17,26.”
From Manumycin polyketides act as molecular glues between UBR7 and P53 (2020) · cites this paper as [2]
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
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
Berman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009) · Journal of Computational Chemistry · doi:10.1002/jcc.21256 · Cited by 26,294
Self-citationBLAST+: architecture and applications
Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., & Madden, T. L. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-421 · Cited by 22,074
Open Babel: An open chemical toolbox
O'Boyle, N. M., Banck, M. S., James, C. A. J., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011) · Journal of Cheminformatics · doi:10.1186/1758-2946-3-33 · Cited by 10,745
The I-TASSER Suite: protein structure and function prediction
Yang, J., Yan, R., Roy, A., Xu, D., Poisson, J., & Zhang, Y. (2015) · Nature Methods · doi:10.1038/nmeth.3213 · Cited by 5,596
UniProt: a hub for protein information
The UniProt Consortium (2015) · Nucleic Acids Research · doi:10.1093/nar/gku989 · Cited by 5,106
Hopkins, A. L., & Groom, C. R. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd892 · Cited by 3,305
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
DrugBank 4.0: shedding new light on drug metabolism
Law, V., Knox, C., Djoumbou-Feunang, Y., Jewison, T., Guo, A. C., Liu, Y., Maciejewski, A., Arndt, D., Wilson, M., Neveu, V., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1068 · Cited by 1,995
Flagged first, then by citations
Cited by
Sorted by citations
Items 801–900 of 953
Shuken, S. R., Frere, G. A., Beard, C. R., Canterbury, J. D., Zuniga, N. R., Gassaway, B. M., Dawson, S. L., Ooi, K. H., Paulo, J. A., McNerney, M. W., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.10.675380 · Cited by 1
“…sites that are known to be reactive to at least one of the electrophilic scout fragments KB02 and KB05 (as positive controls), totaling 300 sites; 30,31 next, we targeted 199 cysteines on proteins in the macroautophagy pathway and 138 in the MAPK cascade using the QuickGO web tool as described…”
Tryptoline Stereoprobe Elaboration Identifies Inhibitors of the GRPEL1-HSPA9 Chaperone ComplexPreprint
Hayward, R. E., Berkeley, R. F., Gao, Z., Garhammer, M., Morizono, M. A., Njomen, E., Li, H., DeMeester, K. E., Cociorva, V., Herzik, M. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.20.683548 · Cited by 1
Self-citationGrams, R. J., Murtagh1, O. L., Ware, M. L., Vasylevskyi, S., & Hsu, K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.27.702106 · Cited by 1
“28 20, 29 , 38 Rare examples like a chiral sulfonimidoyl fluoride demonstrate that chirality at the electrophilic center”
Cheng, R., Lin, H., Yu, X., Misra, S., Mitchell, A. D., Woyach, J. A., Qi, X. L., & Wang, J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.14.705950 · Cited by 2
“Covalent warheads are powerful tools for achieving strong and durable target engagement, particularly at shallow or cryptic binding sites 11–20 .”
ESCAPE: assigning site-specific activity to covalent ligands in cells by prime editingPreprint
Tse, J., Brothers, W. R., Hayward, R. E., Barbas, S., Sheng, K., Spencer, K. R., DeMeester, K. E., Njomen, E., Williamson, J. R., Liu, D. R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.28.741261 · Cited by 1
Self-citationWas genau machen reaktive Fragmente eigentlich in Zellen?
Plettenburg, O. (2016) · Angewandte Chemie · doi:10.1002/ange.201607914
Johnston, A. (2017) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-6065
Investigating Dysregulated Metabolic Pathways that Drive Cancer Pathogenicity
Roberts, L. S. (2017) · eScholarship (California Digital Library)
Recent advances of chemical proteomics for protein drug target screening
Zhang, X., Hu, L., & Zhang, W. (2017) · Scientia Sinica Vitae · doi:10.1360/n052017-00153
Yang, Y. (2017) · Digital Repository Service (Northeastern University) · doi:10.17760/d20260848
“23E+10 20% HC (360-374)/HC N-terminal (1-16) # 6.”
BackgroundMethodInfluential2-Acryloyl-4,5-methylenedioxyphenol: A Small Molecule Endowed with Antidermatophytic Activity
Zuccolo, M., Dallavalle, S., Cincinelli, R., Mattio, L. M., Mazzini, S., Cesare, M. D., & Musso, L. (2018) · Letters in Drug Design & Discovery · doi:10.2174/1570180815666180803115347
“Numerous research groups are currently involved in developing specific covalently binding inhibitors [16] and many approaches based on the use of covalent fragments as a starting point for lead-generation campaigns have been published to date [20, 21].”
BackgroundA Dual‐Purpose Bromocoumarin Tag Enables Deep Profiling of the Cellular Cysteinome
Rabalski, A. J., Williams, J. D., McClure, R. A., Vasudevan, A., & Baranczak, A. (2019) · PROTEOMICS · doi:10.1002/pmic.201800433
In Vivo Targeting of Endogenous Proteins with Reactive Small Molecules
Shindo, N., & Ojida, A. (2019) · Wiley eBooks · doi:10.1002/9783527344406.ch10
Development of an aptamer based lateral flow test strip for a diabetes biomarker
Moabelo, K. L. (2019) · University of the Western Cape Electronic Theses and Dissertations Repository (University of the Western Cape)
Lin, Z., Wang, X., Bustin, K. A., He, L., Suciu, R. M., Schek, N., Ahmadi, M., Hu, K., Olson, E. J., Parsons, W. H., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.17.154864
Squaric ester applications as novel lysine electrophiles in molecular probe design
Ho, J. S. (2020) · DSpace@MIT (Massachusetts Institute of Technology)
α-Methylene-β-Lactone Probe for Measuring Live-Cell Reactions of Small MoleculesPreprint
Wang, L., Riel, L. P., Bajrami, B., Deng, B., Howell, A. R., & Yao, X. (2020) · ChemRxiv · doi:10.26434/chemrxiv.12078582.v1
Trendbericht Biochemie: Kovalente Proteinliganden
Hacker, S. M. (2021) · Nachrichten aus der Chemie · doi:10.1002/nadc.20214111122
DRIVES FOR REACTOR-CONTROL-RODS. A SURVEY OF THE BASIC PRINCIPLES AND THEIR REALIZATIONS
Schallopp, B. (1963) · OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information)
Abegg, D., Tomanik, M., Qiu, N., Pechalrieu, D., Shuster, A., Commare, B., Togni, A., Herzon, S. B., & Adibekian, A. (2021) · doi:10.33774/chemrxiv-2021-2001z
Utility of chemical probes for mass spectrometry based chemical proteomics
Bajrami, B., Martin, J. G., & Johnson, D. S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821433-6.00003-9
Introduction to proteomics for chemical biology
Wang, L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821433-6.00005-2
"El soneto a Granada" de Pablo Antonio Cuadrado
Urbina, N. (2010) · Hispanic poetry review
O cenotáfio de Newton de Étienne Louis Boullée - 1784 - como planetário
dos Reis, V. (2012)
Structure-Based Survey of the Human Proteome for Opportunities in Proximity PharmacologyPreprint
Rovers, E., & Schapira, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.13.475779
Zhuang, Z., & Gui, W. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735998265.793563718
Cysteinyl Proteomes: Exotic Modifications
(2020) · Royal Society of Chemistry eBooks · doi:10.1039/9781839161841-00358
Targeting the undruggable proteome
(2016) · Nature Methods · doi:10.1038/nmeth.3941
Chiang, C. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735998607.793561779
A Chemical Proteomic Probe for the Mitochondrial Pyruvate Carrier Complex
Yamashita, Y., Vinogradova, E. V., Zhang, X., Suciu, R. M., & Cravatt, B. F. (2019) · Angewandte Chemie · doi:10.1002/ange.201914391
Self-citationα-Methylene-β-Lactone Probe for Measuring Live-Cell Reactions of Small MoleculesPreprint
Wang, L., Riel, L. P., Bajrami, B., Deng, B., Howell, A. R., & Yao, X. (2020) · ChemRxiv · doi:10.26434/chemrxiv.12078582
“With its broad reactivity, the MeLac warhead also offers a unique possibility to convert non-covalent inhibitors to measurement probes targeting different enzymes,(34) as well as to broaden druggable targets by identifying new binding sites.(6-7) MeLac probes, being useful for live-cell applications, potentially have…”
BackgroundMethodInfluentialStieger, C. E., Park, Y. H., de Geus, M. A. R., Kim, D., Huhn, C., Slenczka, J. S., Ochtrop, P., Müchler, J. M., Süßmuth, R. D., Broichhagen, J., et al. (2022) · Angewandte Chemie · doi:10.1002/ange.202205348
A stable α-lactam reagent for bioconjugation and proteomic profilingPreprint
Mahía, A., Kiib, A. E., Nišavić, M., Palmfeldt, J., & Poulsen, T. B. (2022) · ChemRxiv · doi:10.26434/chemrxiv-2022-p4wtd
Yang, F., & Wang, C. (2022) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2022.07.037
Kostić, M., & Jones, L. H. (2022) · Wiley eBooks · doi:10.1002/9781119774198.ch15
Identification of Covalent Ligands – from Single Targets to Whole Proteome
Ngo, C., Ekanayake, A. I., & Zhang, C. (2023) · Israel Journal of Chemistry · doi:10.1002/ijch.202200105
A chemoproteomic platform for reactive fragment profiling against the deubiquitinasesPreprint
Cookson, R., Vuorinen, A., Pettinger, J., Kennedy, C. R., Kirkpatrick, J. M., Heap, R. E., Powell, A. J., Snijders, A. P., Skehel, M. J., House, D., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.01.526632
“17, 18, 30, 31 Importantly, this would enable profiling of target engagement of endogenous proteins in their native context, where protein-protein interactions, post-translational modifications and subcellular localisation alter their activities and ligandability.”
Small-molecule trapping of an RNA-binding protein blocks cancer cell growth
(2023) · Nature Chemical Biology · doi:10.1038/s41589-023-01271-z
Burton, N. R., Polasky, D. A., Shikwana, F., Ofori, S., Yan, T., Geiszler, D., Leprevost, F. D. V., Nesvizhskii, A. I., & Backus, K. M. (2023) · ChemRxiv · doi:10.26434/chemrxiv-2023-n8h29-v3 · Cited by 1
Self-citationZerhouni, M., Martin, A. R., Furstoss, N., Gutierrez, V. S., Jaune, E., Tekaya, N., Béranger, G. E., Abbe, P., Regazzetti, C., Amdouni, H., et al. (2023) · doi:10.1158/0008-5472.c.6513040.v1
Activity‐Based Protein Profiling – Celebrating the Groundbreaking Contributions of Benjamin Cravatt
Weerapana, E., & Hacker, S. M. (2023) · Israel Journal of Chemistry · doi:10.1002/ijch.202300059
α‐Lactam Electrophiles for Covalent Chemical Biology**
Mahía, A., Kiib, A. E., Nišavić, M., Svenningsen, E. B., Palmfeldt, J., & Poulsen, T. B. (2023) · Angewandte Chemie · doi:10.1002/ange.202304142
Pairs of Triazole-Based Isomeric Covalent Inhibitors with Tunable Reactivity and SelectivityPreprint
Zhang, C., Xu, S., Ye, Z., Shang, S., Wang, F., Zhang, H., Chen, L.-G., Lin, H., Chen, C., & Hua, F. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4460012
Richard Lerner's Bioinspiration: Biomolecular Visualization and Modeling at Scripps Research
Olson, A. J., Sanner, M. F., Goodsell, D. S., & Forli, S. (2023) · Israel Journal of Chemistry · doi:10.1002/ijch.202300055
Self-citationChemistry of Covalent Drugs: Chemical Reactions with Endogenous Proteins in Live Cells
Shindo, N., & Ojida, A. (2024) · Journal of Synthetic Organic Chemistry Japan · doi:10.5059/yukigoseikyokaishi.82.50
Synthesis and biological evaluation of vioprolide B and its dehydrobutyrine-glycine analogue
Reineke, N. O., Elsen, F. A. V., Grab, H. A., Mostert, D., Sieber, S. A., & Bach, T. (2024) · Chemical Communications · doi:10.1039/d4cc02946a
Emerging Technologies for Epigenetic Drug Discovery
(2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781837674916-part2
Mass Spectrometry and Chemical Biology Approaches for Deconvoluting Epigenetic Targets
Burton, A. J., Hamza, G. M., Iannetta, A. A., Miele, E., & Zhang, A. X. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781837674916-00050
Charting the ligandable proteome for stereoselective interactions
Pezacki, J. P., Lundrigan, E., Evers, P., & Uguccioni, S. M. (2024) · Nature Chemistry · doi:10.1038/s41557-024-01639-1
Jackson, P. A., Kisty, E. A., Pradhan, V., Swank, C., Bohrer, L., Nolan, T. L., Weerapana, E., & Lapinsky, D. J. (2024) · ACS Omega · doi:10.1021/acsomega.4c06879
Stressing out with electrophiles
Stanton, C. R., Nutsch, K., & Bollong, M. J. (2024) · Nature Chemical Biology · doi:10.1038/s41589-024-01749-4
Covalency in PROTACs: Mechanisms and applications
Geiger, T. M., & Nowak, R. P. (2024) · Annual reports in medicinal chemistry · doi:10.1016/bs.armc.2024.10.001
Protein‐metabolite Interactions Based on Chemical Targeting Methods
Sun, S., Li, C., Hou, H., & Li, J. (2024) · ChemBioChem · doi:10.1002/cbic.202400852
An activation-based high throughput screen identifies caspase-10 inhibitors
Castellón, J. O., Yuen, C., Han, B., Andrews, K. H., Ofori, S., Julio, A. R., Boatner, L. M., Palafox, M. F., Perumal, N., Damoiseaux, R. D., et al. (2025) · RSC Chemical Biology · doi:10.1039/d5cb00017c
“27,28 Despite these advances, obtaining highly selective inhibitors remains challenging, likely due in large part to the high sequence and structural homology of all caspases.”
Self-citationNikolova, V., Linnemannstöns, K., Zahoruiko, A., Ganter, M., Lüder, C. G. K., & Dobbelstein, M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.14.643256
Kline, G. M., Boinon, L., Guerrero, A. M., Kutseikin, S., Cruz, G., Williams, M. P., Paxman, R. J., Balch, W. E., Kelly, J. W., Mu, T., et al. (2026) · eLife · doi:10.7554/elife.107000.3
PSL Chemical Biology Symposia: The Increasing Impact of Chemistry in Life Sciences
Sastourné‐Haletou, R., Marynberg, S., Pereira, A. P. D. A., Su, F., Chen, M., Valet, G., Sindikubwabo, F., Cañeque, T., Müller, S., Colombeau, L., et al. (2025) · ChemBioChem · doi:10.1002/cbic.202500231
Recent highlights in covalent inhibitor design
Marino, K. A., Nicewonger, R., Zhang, H., & Thorarensen, A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00010-8
Chemoproteomics Approaches for Diverse Modalities
Eberl, H. C., Knecht, S., Queisser, M. A., & Bantscheff, M. (2025) · Wiley eBooks · doi:10.1002/9781394236145.ch19
Peng, Q., & Weerapana, E. (2025) · Methods in molecular biology · doi:10.1007/978-1-0716-4502-4_4
Kalpage, H. A., Chi, A., & Bodea, S. (2025) · Methods in molecular biology · doi:10.1007/978-1-0716-4502-4_17
Activity-Based Protein Profiling for Functional Cysteines and Protein Target Identification
Koo, T.-Y., & Chung, C. Y. (2025) · Methods in molecular biology · doi:10.1007/978-1-0716-4502-4_18
Expanding the repertoire of chemically induced covalent neoantigens
Zhou, C., Jin, X., Huang, W., Wu, H., McGregor, L. M., Schirle, M., Zhang, C., & Zhang, X. (2026) · Nature Chemical Biology · doi:10.1038/s41589-026-02280-4
Cobley, J. N. (2025) · Preprints.org · doi:10.20944/preprints202507.2120.v2
Kline, G. M., Boinon, L., Guerrero, A. M., Kutseikin, S., Cruz, G., Williams, M. P., Paxman, R. J., Balch, W. E., Kelly, J. W., Mu, T., et al. (2025) · eLife · doi:10.7554/elife.107000
“…the quinone methide of AA263 seems unlikely to be the main pathway of electrophile formation from AA263 given the remarkable preference of AA263 to react with ER-localized proteins, which is not a general feature of other small molecule electrophiles ( Backus et al., 2016 ; Paxman et al., 2018 ).”
Kline, G. M., Boinon, L., Guerrero, A. M., Kutseikin, S., Cruz, G., Williams, M. P., Paxman, R. J., Balch, W. E., Kelly, J. W., Mu, T., et al. (2025) · eLife · doi:10.7554/elife.107000.1
Scaling Covalent Ligand Discovery via Library-Versus-Proteome ScreeningPreprint
Huang, Y., Hou, L., He, R., Zhu, L. F., Xu, C., Duan, S., Hu, J. Z., Yang, X., Tsai, Y., Wang, C., et al. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5397846
A Warm Welcome to MedChem: The Frontiers in Medicinal Chemistry 2025
Schiedel, M., Pinto, M., Lopez, A. U., Barbie, P., Pape, F., Tarasewicz, A., Heßler, G., Gmeiner, P., Lamers, C., & Gehringer, M. (2025) · ChemMedChem · doi:10.1002/cmdc.202500609
O’Hare, S., Tolmachova, K. A., & Bode, J. W. (2025) · ACS Chemical Biology · doi:10.1021/acschembio.5c00281
Illuminating the Ligandable Human Proteome with AI Protein ProfilingPreprint
Dayhoff, G. W., Kortzak, D., Shen, M., Liu, R., Lin, J., Zhang, Z., & Shen, J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.07.670677
A pipeline for proteome-wide analysis of electrophile selectivity
Jo, J., & Bogyo, M. S. (2025) · Nature Chemistry · doi:10.1038/s41557-025-01906-9
Munugoda, U., Gilpatrick, S. T., Das, D., Parkin, S., Miller, A., & Awuah, S. G. (2025) · Angewandte Chemie · doi:10.1002/ange.202516331
Kline, G. M., Boinon, L., Guerrero, A. M., Kutseikin, S., Cruz, G., Williams, M. P., Paxman, R. J., Balch, W. E., Kelly, J. W., Mu, T., et al. (2025) · eLife · doi:10.7554/elife.107000.2
Navarrete-Perea, J., Mirhadi, S., Li, J., Mitchell, D. C., Dhillon, S., Gerkman, R., Bodea, S., & Chi, A. (2025) · Analytical Chemistry · doi:10.1021/acs.analchem.5c04756
Tao, Y., Wang, L., Huang, X., Wen, F., Tan, X., Zhu, Y., Sun, J., Wan, X., Tian, X., Guo, T., et al. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.109490
Jarvis, A. F., Bhat, M. Y., Maujean, T., Abreu, A. L., Toy, K., Burslem, G. M., & Brady, D. C. (2026) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.5c00231
Emerging Trends in Analytical Chemistry for Measuring Dynamic Biological Functions
Tainaka, K. (2025) · BUNSEKI KAGAKU · doi:10.2116/bunsekikagaku.74.717
Structure-guided discovery strategies for Trop2-targeted small molecule inhibitors
Moon, D. O. (2026) · Bulletin du Cancer · doi:10.1016/j.bulcan.2025.11.016
Mapping ortholog-restricted ligandable cysteines in the wheat pathogen Zymoseptoria triticiPreprint
Yoo, M., Ware, T. B., Moschen, S., Reed, A., Reinhardt, C. J., Njomen, E., Thacker, U., Melillo, B. N., Scalliet, G., Paşcanu, V., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.16.706151
Self-citationMultivalent Probes for Exploring Carbohydrate Binding Proteins
Kamoshita, S., & Sakurai, K. (2026) · Springer eBooks · doi:10.1007/978-981-95-5335-8_10
Tian, K., Zhou, J., Li, Y., Li, J., Yue, X., Qiao, X., Qin, H., & Ye, M. (2026) · Analytical Chemistry · doi:10.1021/acs.analchem.5c03505
Kim, J., Correy, G. J., Hall, B. W., Rachman, M. M., Mailhot, O., Togo, T., Gonciarz, R. L., Jaishankar, P., Neitz, R. J., Hantz, E. R., et al. (2026) · eLife · doi:10.7554/elife.110475
Chemical probes to interrogate biological systems
Ende, C. W. A., Field, S. D., Majmudar, J. D., & Schenone, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00055-8
Lysine Oxidase: An Enzyme to Control Biofilm, Survey, and Analysis
Bisht, N., Karn, S. K., & Raj, V. (2026) · Industrial Biotechnology · doi:10.1177/15509087261429854
“66 In this study, more than 9,000 lysines were quantified in the cells of human proteomes and several hundred residues with increased reactivity were identified.”
Chesti, J., Miles, J. A., Wade, G. J., Grossman, S., Preston, G. W., Bayliss, R. W., Warriner, S. L., Wright, M. H., & Nelson, A. S. (2026) · Chemistry - A European Journal · doi:10.1002/chem.202600009
Jones, H. B. L., Draganov, S. D., Huamán, S. S., Wing, P. A. C., Nguyen, C., Liang, Z., Dörner, J., Lithgow, J., Murphy, E. J., Beard, A., et al. (2026) · npj Drug Discovery. · doi:10.21203/rs.3.rs-9106698/v1
4-Oxo-2-Nonenal Crosslinks Vicinal Cysteine-Lysine Pairs in Cellular Proteins
Cheng, R., Wang, M., Liu, K., Fu, L., Xu, P., Tian, C., & Yang, J. H. (2026) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2026.101573
Coleman, P., Laddach, A., Anderson, R., Yang, X., Kumar, R., Shah, A. M., Fraternali, F., & Burgoyne, J. R. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104196
Proteolysis‐Assisted Cyclization Facilitates Site‐Centric Target Deconvolution of Isothiocyanates
He, J., Tian, C., Li, Q., Zhang, J., He, J., Zhang, L., Lei, X., & Yang, J. H. (2026) · Angewandte Chemie · doi:10.1002/ange.5512891
Zhu, Y. (2026) · STAR Protocols · doi:10.1016/j.xpro.2026.104567
“27 Database searching in targeted-protein workflows involves two conceptually distinct layers: (1) definition of the protein sequence database and (2) construction of the modification search space.”
SuFEx‐Enabled Reprogramming of Flavonoids for Selective α‐Glucosidase Covalent Inhibition
Guo, F., Zhang, L., Wang, M., Du, Y., Zhang, T., Chen, H., Sun, J., Yu, Y., He, Z., An, J., et al. (2026) · Advanced Science · doi:10.1002/advs.75869
“A central challenge in covalent inhibitor design is the careful selection of the electrophilic warhead, which governs target specificity, reaction kinetics, and overall therapeutic window [ 12, 13 ].”
Yang, K., Li, S., Li, B., Richards, D. M., Dong, K., Seneviratne, U. I., Lee, W., Iannetta, A. A., Xu, H., Gygi, S. P., et al. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.6c00101
Yin, J.-J., Xin, S., Cao, H., & Zhang, L. (2026) · Nature Chemistry · doi:10.1038/s41557-026-02156-z
“On this designed platform, a series of peptides ( 58–60 ) composed of natural amino acids, including alanine, glycine and valine, was subjected to optimal reaction conditions and functioned smoothly.”
Wilders, H., Grant, E. K., & Bush, J. T. (2026) · Nature Chemical Biology · doi:10.1038/s41589-026-02242-w
Raguseo, F., Fellows, E., de Chiara, C., Mortishire-Smith, B. J., Segura‐Bayona, S., Cawood, E. E., Jiang, M., Subtil, F. T., Idilli, A. I., McCarthy, W. J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.10.731339
“…fragment – chemoproteomics screening has emerged as a useful strategy for identifying small molecule binders across the proteome, expanding the set of proteins for which actionable chemical starting points are available, including targets historically considered difficult to drug 15,16 , 17 .”
Proteomics‐Driven Strategies for Proximity‐Inducing Drug Discovery
Fan, R., Ni, J., Zhou, T., Jiang, H. Q., Zhao, W., & Tan, M. (2026) · Angewandte Chemie · doi:10.1002/ange.3307512
Unique Cysteine-Directed Covalent Inhibition of PRMT1 Suppresses Breast Tumorigenesis
Shao, M., Li, R., Hu, J. B., Xi, W., Mutyala, R., Guan, L., Huang, C., Sun, R., Yang, X., 靳博, et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00262
Date, A., Schuhmacher, A., Lü, J., Berezina, D., Tate, E. W., Barnard, A., & Houghton, J. W. (2026) · PROTEOMICS · doi:10.1002/pmic.70154
“Labelling is achieved through covalent warheads [ 3 ], photo-crosslinking [ 4 ], or metabolic incorporation [ 5 ], and is followed by the pull-down of labelled targets by leveraging enrichment moieties such as clickable tags.”
Metadata
- Authors
- 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., Wolan, D. W., & Cravatt, B. F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Backus, Keriann M.
- Cravatt, Benjamin F.
- ORCID
- Venue
- Nature
- Published
- 2016-06-15
- Volume
- 534
- Issue
- 7608
- Pages
- 570-574
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4919207
- OpenAlex
- W2430132928
- Cited by
- 940
- References
- 43
- Citations by year
- 2026: 109 · 2025: 114 · 2024: 114 · 2023: 134 · 2022: 82 · 2021: 94 · 2020: 87 · 2019: 69 · 2018: 61 · 2017: 54 · 2016: 18
- FWCI
- 31.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Cancer Institute (CA-087660, R37CA087660, R01CA087660)
- National Institute of General Medical Sciences (GM069832, GM-090294, GM108208, R01GM090294, F32GM108208, R01GM069832)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- covalent ligands, chemical probes, undruggable proteins, transcription factors, caspase-8, caspase-10, extrinsic apoptotic pathway, T cells, protein function
- MeSH terms
- Cells, Cultured, Cysteine, Drug Evaluation, Preclinical, Enzyme Precursors, Humans, Ligands, Peptide Fragments, T-Lymphocytes, Transcription Factors, Apoptosis, Proteome, Caspase 8, Caspase 10, Small Molecule Libraries
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
