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
Cited by
Sorted by citations
Items 601–700 of 953
Boatner, L. M., Eberhardt, J., Shikwana, F., Holcomb, M., Lee, P., Houk, K. N., Forli, S., & Backus, K. M. (2025) · ACS Chemical Biology · doi:10.1021/acschembio.5c00225 · Cited by 6
Self-citationWarhead Strategy for Targeted Protein S-Nitrosation
Zhang, C., Ye, H., Ji, D., Xiong, T., Yu, J., Qian, Z., Li, C., Li, H., Liang, Z., Zhang, Y., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c07409 · Cited by 6
The Expanding E3 Ligase-Ligand Landscape for PROTAC Technology
Li, Z., Huang, X., Zhao, X., Zhang, Y., & Li, P. (2025) · Targets · doi:10.3390/targets3040030 · Cited by 9
A perspective on cysteine-reactive activity-based probes
Nuber, C. M., Schwab, M. A., & Konrad, D. B. (2025) · Organic & Biomolecular Chemistry · doi:10.1039/d5ob00905g · Cited by 6
Munugoda, U., Gilpatrick, S. T., Das, D., Parkin, S., Miller, A., & Awuah, S. G. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202516331 · Cited by 6
Regulation of RNA-binding proteins by small biomolecules
Miao, W., Porter, D. F., Lopez-Pajares, V., & Khavari, P. A. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00914-4 · Cited by 7
“Similarly, isotopic tandem orthogonal proteolysis-activity-based protein profiling (isoTOP-ABPP) has been applied to reactive cysteine 326,327 and lysine 328 , enabling quantitative determination of binding sites.”
The limitations of small molecule and genetic screening in phenotypic drug discovery
Vincent, F., & Gianni, D. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.10.008 · Cited by 6
Scinto, S. L., Makara, C. A., Nguyen, M., Ramaraj, P. K., Xie, Y., Thorpe, C., West, G. M., Ende, C. W. A., Xu, Y., & Fox, J. M. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.5c20309 · Cited by 8
Advances in Activity‐Based Protein Profiling of Functional Tyrosines in Proteomes
Brulet, J. W., Ciancone, A. M., Yuan, K., & Hsu, K. (2023) · Israel Journal of Chemistry · doi:10.1002/ijch.202300001 · Cited by 6
Shikwana, F., Heydari, B. S., Ofori, S., Truong, C. C., Turmon, A. C., Darrouj, J., Holoidovsky, L., Gustafson, J. L., & Backus, K. M. (2024) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2024.100898 · Cited by 8
“S14), which are also identi fi ed as very ligandable by prior studies (3, 68).”
InfluentialSelf-citationThe recent advance of PROTACs targeting BCR-ABL for the treatment of chronic myeloid leukemia
Qian, Z., Bai, Y., Zhou, W., Zhang, S.-N., Li, J.-Y., Sun, Q., Wang, Y., Wang, D.-S., Liu, H., Yuan, S., et al. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.108189 · Cited by 7
Chemical Biology Tools for Protein Lysine Acylation
Xie, Y., Du, S., Liu, Z., Liu, M., Xu, Z., Wang, X., Kee, J. X., Yi, F., Sun, H., & Yao, S. Q. (2022) · Angewandte Chemie · doi:10.1002/ange.202200303 · Cited by 6
Suto, N., Kamoshita, S., Hosoya, S., & Sakurai, K. (2021) · Angewandte Chemie · doi:10.1002/ange.202104347 · Cited by 6
Measurement and utilization of the proteomic reactivity by mass spectrometry
Punzalan, C., Wang, L., Bajrami, B., & Yao, X. (2023) · Mass Spectrometry Reviews · doi:10.1002/mas.21837 · Cited by 7
APR-246 increases tumor antigenicity independent of p53
Michels, J., Venkatesh, D., Liu, C., Budhu, S., Zhong, H., George, M. M., Thach, D., Yao, Z., Ouerfelli, O., Liu, H., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202301999 · Cited by 6
“The human proteome contains many cysteines that are potential ligands, revealing that covalent chemistry can be used to expand the druggable component of the human proteome (Backus et al, 2016).”
BackgroundHeterogeneous adaptation of cysteine reactivity to a covalent oncometabolite
Perez, M., Bak, D. W., Bergholtz, S. E., Crooks, D. R., Arimilli, B. S., Yang, Y., Weerapana, E., Linehan, W. M., & Meier, J. L. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ac120.014993 · Cited by 6
Inducible Protein Degradation to Understand Genome Architecture
Tallan, A. M., & Stanton, B. Z. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00306 · Cited by 6
A Paal–Knorr agent for chemoproteomic profiling of targets of isoketals in cells
Wang, M.-R., He, J., He, J.-X., Liu, K., & Yang, J. H. (2021) · Chemical Science · doi:10.1039/d1sc02230j · Cited by 7
Strategic Design of Catalytic Lysine‐Targeting Reversible Covalent BCR‐ABL Inhibitors**
Quach, D., Tang, G., Anantharajan, J., Baburajendran, N., Poulsen, A., Wee, J. L. K., Retna, P., Li, R., Liu, B., Tee, D. H. Y., et al. (2021) · Angewandte Chemie · doi:10.1002/ange.202105383 · Cited by 7
Zhu, H., Mellors, J. S., Chan, W. C., Thompson, J. W., Ficarro, S. B., Tavares, I., Bratt, A. S., Decker, J., Krause, M., Kruppa, G. H., et al. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.2c01337 · Cited by 5
Scaling Proteome-Wide Reactions of Activity-Based Probes
Li, S., Diego, P. A., Bajrami, B., Keshipeddy, S. K., Lam, Y., Deng, B., Farrokhi, V., McShane, A. J., Nemati, R., Howell, A. R., et al. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b01184 · Cited by 6
Chemoproteomic-Driven Discovery of Covalent PROTACs
Zhou, Y., & Xiao, Y. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00795 · Cited by 6
A CRISPR activation screen identifies FBXO22 as an E3 ligase supporting targeted protein degradationPreprint
Basu, A. A., Zhang, C., Riha, I. A., Magassa, A., Ko, F., & Zhang, X. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.15.557708 · Cited by 6
“Using competitive cysteine-directed activity-based protein profiling (ABPP), a chemical proteomic technology for the measurement of target engagement 29,30 , we sought to quantify the degree of blockade of iodoacetamide-desthiobiotin (IA-DTB)-modified cysteines on FBXO22.”
BackgroundUnlocking DCAFs To Catalyze Degrader Development: An Arena for Innovative Approaches
Miao, Q., Kadam, V. D., Mukherjee, A., Tan, Z., & Teng, M. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01209 · Cited by 7
A platform for mapping reactive cysteines within the immunopeptidome
Zhang, C., Chen, Z., Magassa, A., Jin, X., Fang, D., & Zhang, X. (2024) · Nature Communications · doi:10.1038/s41467-024-54139-8 · Cited by 6
“Cysteine-directed ABPP platforms have not only provided comprehensive maps of reactive cysteines across the human proteome, but also advanced investigations into electrophilic small molecule-cysteine interactions for novel ligand discovery 19, 48 .”
BackgroundFree Energy Perturbation and Free-Energy Calculations Applied to Drug Design
Antunes, D., Santos, L. H., Guimarães, A. C. R., & Caffarena, E. R. (2024) · Computer-aided drug discovery and design · doi:10.1007/978-3-031-76718-0_10 · Cited by 6
Towards site-specific manipulation in cysteine-mediated redox signaling
Yang, J. H. (2025) · Chemical Science · doi:10.1039/d5sc02016f · Cited by 5
“41 48 Moreover, this strategy has also been adapted by targeting other amino acid residues including lysine, 46,49 – 51 tyrosine, 52 – 54 serine, 55 aspartate and glutamate, 56 and extends beyond cysteine as a source for TCI development.”
Prioritizing disease-associated missense variants with chemoproteomic-detected amino acids
Palafox, M. F., Boatner, L. M., Wilde, B. R., Christofk, H. R., Backus, K. M., & Arboleda, V. A. (2025) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2025.04.017 · Cited by 6
Self-citationBourne, C. M., Raniszewski, N. R., Mahale, A. B., Kulkarni, M., Exconde, P. M., Liu, S., Yost, W., Wrong, T. J., Patio, R. C., Kardhashi, M., et al. (2025) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.4c00146 · Cited by 7
Potent Inducers of Paraptosis through Electronic Tuning of Hemicyanine Electrophiles
Tamez‐Fernández, J. F., Steven, C. F., Nguyen, J., & Rivera‐Fuentes, P. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c07109 · Cited by 5
Normalizing Covalent Potency for Electrophilicity with Ligand Reactivity Efficiency
Horning, B. D., Kingston, C., Simon, G. M., Patricelli, M. P., Weinstein, D. S., & Cook, B. N. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01803 · Cited by 8
Self-citationEngineering Polymeric Nano-PROTAC for Targeted Protein Degradation and Cancer Therapy
Saeed, M., Amina, Z., Xu, Z., & Yu, H. (2026) · Polymer science & technology. · doi:10.1021/polymscitech.5c00122 · Cited by 5
Development of Lysine Crotonyl‐Mimic Probe to Covalently Identify H3K27Cr Interacting Proteins
Guo, X., Wang, Y., An, Y., Liu, Z., Liu, J., Chen, J., Zhan, M., Liang, M., Hou, Z., Wan, C., et al. (2023) · Chemistry - A European Journal · doi:10.1002/chem.202301624 · Cited by 5
Ghorbani, F., You, S., Grabovyi, G. A., Hong, M., Lindsey, G. L., Chatterjee, A. K., & Bollong, M. J. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c05711 · Cited by 5
Wang, L., Riel, L. P., Bajrami, B., Deng, B., Howell, A. R., & Yao, X. (2020) · ChemBioChem · doi:10.1002/cbic.202000605 · Cited by 7
Hong, S. H., Xi, S. Y., Johns, A. C., Tang, L. C., Li, A., Hum, M. N., Chartier, C. A., Jovanović, M., & Shah, N. H. (2023) · ChemBioChem · doi:10.1002/cbic.202200706 · Cited by 5
Jiang, Z., Tang, Y., Lu, J., Xu, C., Niu, Y., Zhang, G., Yang, Y., Cheng, X., Tong, L., Chen, Z., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102969 · Cited by 5
Galan, S. R. G., Raj, R., Mamalis, D., Jones, L. H., Mohammed, S., & Davis, B. G. (2023) · Chemical Science · doi:10.1039/d3sc04631a · Cited by 5
“32,39 We have previously demonstrated that a method of ‘ reactive accessibility ’ analysis 40 allows useful prediction of the regiose-lectivity of chemistries in protein substrates containing multiply addressable functional groups, in that case multiple azides in a protein with multiple unnatural…”
Chemical proteomics to study metabolism, a reductionist approach applied at the systems level
Ali, M. Y., & Bar‐Peled, L. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.02.015 · Cited by 5
Doak, B. C., Whitehouse, R. L., Rimmer, K. A., Williams, M. L., Heras, B., Caria, S., Ilyichova, O. V., Vazirani, M., Mohanty, B., Harper, J. B., et al. (2024) · ChemMedChem · doi:10.1002/cmdc.202300684 · Cited by 6
“(10) SAR for replacement of the amino substituent (4-17), the expansion of the methyl amino substituent (18-49) and optimization of the aromatic core (50-65) were explored and characterization of their binding using HSQC NMR spectroscopy and X-ray crystallography was conducted.”
BackgroundMethodFunctional Proteomics Driven by Chemical and Computational Approaches
Chen, Y., Qin, W., & Wang, C. (2021) · Chinese Journal of Chemistry · doi:10.1002/cjoc.202100785 · Cited by 5
Clickable report tags for identification of modified peptides by mass spectrometry
Makarov, D., Telek, A., Becker, T., von Wrisberg, M., Schneider, S., & Kielkowski, P. (2022) · Journal of Mass Spectrometry · doi:10.1002/jms.4812 · Cited by 5
Uncovering an overlooked consequence of phosphorylation: change in cysteine reactivity
Lakemeyer, M., & Bogyo, M. S. (2022) · Nature Methods · doi:10.1038/s41592-022-01414-5 · Cited by 5
Li, J., Wang, G., Ye, M., & Qin, H. (2023) · Chinese Journal of Chromatography · doi:10.3724/sp.j.1123.2022.05013 · Cited by 5
Heterocyclic Diaryliodonium-Based Inhibitors of Carbapenem-Resistant Acinetobacter baumannii
Kumari, P., Kaul, G., Kumar, T. A., Akhir, A., Shukla, M., Sharma, S., Kamat, S. S., Chopra, S., & Chakrapani, H. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.04773-22 · Cited by 5
“The samples were resolved and activity was visualized using a 10% SDS-PAGE gel using established protocols (23, 26, 51, 52).”
MethodDifferently Tagged Probes for Protein Profiling of Mitochondria
Dong, J., Hong, D., Lang, W., Huang, J., Qian, L., Zhu, Q. X., Li, L., & Ge, J. (2019) · ChemBioChem · doi:10.1002/cbic.201800735 · Cited by 5
Activity‐Based Protein Profiling
van Rooden, E. J., Bakker, A. T., Overkleeft, H. S., & van der Stelt, M. (2018) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0023406 · Cited by 6
Fullenkamp, C. R., Liang, X., Pettersson, M., & Schneekloth, J. S. (2024) · Methods and principles in medicinal chemistry · doi:10.1002/9783527840458.ch13 · Cited by 5
A covalent inhibitor targeting Cys16 on RhoA in colorectal cancer
Koo, T.-Y., Li, J. Y. K., Lee, N.-S., Chen, J., Yip, H. Y.-Y., Huang, I. B., Ng, K. Y., Yan, H. H. N., Leung, S. Y., Ma, S., et al. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.08.004 · Cited by 5
Yu, H., Zhang, X., Liu, Z., & Zhang, L. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01488 · Cited by 4
Covalent chemistry in targeted protein degradation
Tan, J., Liang, Y., Shao, S., & Shen, Y. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115777 · Cited by 4
Zheng, Z., Cheng, Y., Li, P., & Tan, C. S. H. (2024) · ChemBioChem · doi:10.1002/cbic.202400715 · Cited by 4
Feng, Y., Han, Y., Hu, A., Qu, Y., Hu, Y., Wu, H., Wang, X., & Li, H. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.10.018 · Cited by 4
Application of A lpha F old models in evaluating ligandable cysteines across E 3 ligases
Koldenhof, P., Bemelmans, M. P., Ghosh, B. K., Damm‐Ganamet, K. L., van Vlijmen, H., & Pande, V. (2024) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26675 · Cited by 5
“…such as high throughput screening, chemoproteomics-enabled covalent screening platforms have shown promise for rapid identification of binders for several diverse and underexplored proteins 11 including E3 ligases, and covalent hits have been reported for multiple non VHL and CRBN ligases.”
BackgroundGu, Z., Yan, Y. J., Liu, H., Wu, D., Yao, H., Lin, K., & Li, X. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c01900 · Cited by 4
Xue, J., Li, M., Li, K., Wang, M., Yin, J., Sun, D., Deng, Y., Wei, Q., Wong, J., Zhu, T., et al. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07765-z · Cited by 5
Reaktive chemische Sonden: Jenseits des Kinase‐Cysteinoms
Jones, L. H. (2018) · Angewandte Chemie · doi:10.1002/ange.201802693 · Cited by 4
Chemical Proteomics for Expanding the Druggability of Human Disease
Zhang, X. (2020) · ChemBioChem · doi:10.1002/cbic.202000495 · Cited by 4
Shraga, A., Resnick, E., Gabizon, R., & London, N. (2021) · Annual reports in medicinal chemistry · doi:10.1016/bs.armc.2021.04.001 · Cited by 5
A Cyclopropene Electrophile that Targets Glutathione S‐Transferase Omega‐1 in Cells
Wørmer, G. J., Hansen, B. K., Palmfeldt, J., & Poulsen, T. B. (2019) · Angewandte Chemie · doi:10.1002/ange.201907520 · Cited by 4
Sharma, T., Zhang, Y., Zigrossi, A., Cravatt, B. F., & Kastrati, I. (2023) · Breast Cancer Research and Treatment · doi:10.1007/s10549-023-07037-4 · Cited by 4
Self-citationVirus-like Iron-Gold Heterogeneous Nanoparticles for Drug Target Screening
Tang, J., Sun, Q., Xie, Y., Zheng, Q., & Ding, Y. (2023) · Analytical Chemistry · doi:10.1021/acs.analchem.3c01762 · Cited by 4
Wan, C., Yang, D., Guo, X., Zhang, T., Ruan, Z., Dai, C., Xing, Y., Yin, F., Wang, R. Y., & Li, Z. (2024) · Chemical Communications · doi:10.1039/d4cc00295d · Cited by 4
Systematic Targeting of Protein Complexes with Molecular COUPLrs
Yang, D., Harry, S. A., Chong, H. B., Khandelwal, N., Zhang, E., Nordenfelt, N. S., Chen, N. J., Lee, C., Kaluziak, S. T., Codd, E. M., et al. (2026) · Cancer Discovery · doi:10.1158/2159-8290.cd-25-2314 · Cited by 4
Johnson, D. S., & Majmudar, J. D. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.10.013 · Cited by 4
“…at UC Berkeley have applied the isoTOP-ABPP chemoproteomic method to screen covalent smallmolecule fragments in cells to enable the rapid and coupled discovery and pharmacological interrogation of novel functional binding pockets within the proteome (Anderson et al., 2017; Backus et al., 2016).”
MethodMethodology for Identification of Cysteine-Reactive Covalent Inhibitors
Kathman, S. G., & Statsyuk, A. V. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9187-7_15 · Cited by 4
Contemporary Techniques for Target Deconvolution and Mode of Action Elucidation
Schirle, M., & Jenkins, J. L. (2020) · Royal Society of Chemistry eBooks · doi:10.1039/9781839160721-00083 · Cited by 3
Isobe, Y., Okumura, M., White, R., McGregor, L. M., McKenna, J. M., Tallarico, J. A., Schirle, M., Maimone, T. J., & Nomura, D. K. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/814285 · Cited by 4
Luo, M., Spradlin, J. N., Brittain, S. M., McKenna, J. M., Tallarico, J. A., Schirle, M., Maimone, T. J., & Nomura, D. K. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.12.198150 · Cited by 4
“…cysteine-reactivity of EN219 in situ in 231MFP breast cancer cells by competitive isotopic tandem orthogonal proteolysis-ABPP (isoTOP-ABPP) using previously well-validated methods (Backus et al., 2016; Grossman et al., 2017; Spradlin et al., 2019; Wang et al., 2014; Weerapana et al., 2010).”
MethodMonitoring iron-sulfur cluster occupancy across the E. coli proteome using chemoproteomicsPreprint
Bak, D. W., & Weerapana, E. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.01.438105 · Cited by 4
SP3-FAIMS Chemoproteomics for High Coverage Profiling of the Human CysteinomePreprint
Yan, T., Desai, H., Boatner, L. M., Yen, S., Cao, J., Palafox, M. F., Jami‐Alahmadi, Y., & Backus, K. M. (2020) · ChemRxiv · doi:10.26434/chemrxiv.13487364 · Cited by 4
Self-citationKim, 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.110475.1 · Cited by 7
Structural and mechanistic analysis of covalent ligands targeting the RNA-binding protein NONO
Lindsey, G. L., Hockley, T. K., Gomez, A. V., Marshall, A. C., Brothers, W. R., Finney, C. T., Gross, J., Fox, A. H., Yeo, G. W., Melillo, B., et al. (2026) · Cell Chemical Biology · doi:10.1016/j.chembiol.2025.12.010 · Cited by 6
“28 A full set of CFA stereoisomeric analogs of (R)- and (S)-SKBG-1 was synthesized (Figure 2A, and Data S1) and evaluated for reactivity with NONO by cysteine-directed ABPP 32–35 in the prostate cancer cell line 22Rv1 (20 μM compound, 6 h).”
Self-citationDesign of Entry Inhibitor Peptides Covalently Bonding SARS-CoV-2 Variants in Wastewater
Xue, B., Li, R., Zhu, Q., Yang, Y., Wang, F., Cheng, Z., & Zhou, X. (2025) · Environmental Science & Technology · doi:10.1021/acs.est.5c02307 · Cited by 3
Validation of methods for enriching and detecting SARS-CoV-2 RNA in wastewater
Li, R., Wang, N., Guo, J., Xue, B., Liu, C., Guo, Y., & Zhou, X. (2025) · Environmental Chemistry Letters · doi:10.1007/s10311-025-01843-6 · Cited by 3
Targeting Creatine and Creatine Kinase in Cancer: Exploring Potential Therapeutic Strategies
Abdollahzadeh, M., Ghodsi, R., Taherzadeh, Z., & Hatamipour, M. (2025) · Current Drug Targets · doi:10.2174/0113894501373936250609114913 · Cited by 3
Ferenczy, G. G., & Keserű, G. M. (2025) · Drug Discovery Today · doi:10.1016/j.drudis.2025.104454 · Cited by 3
Xie, Y., Nakano, Y., Tummala, P., Oakley, A. J., Suwandi, A., Cuellar, M. E., Strasser, J. M., Dahlin, J. L., Walters, M. A., Casarotto, M. G., et al. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118072 · Cited by 3
Zhao, W., Tang, Y., Gao, Y., Ding, Q., Li, Q., Li, W., & Lei, X. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202515603 · Cited by 4
Enrichment-Free, Targeted Covalent Drug Discovery in Live Cells
Dong, K. D., Yu, Q., Yang, K., Wong, B. J., Hong, Y., Fu, S., Whitehouse, R. L., Fischer, E. S., & Gygi, S. P. (2025) · ACS Chemical Biology · doi:10.1021/acschembio.5c00581 · Cited by 5
Nuber, C. M., Milton, A. V., Nissl, B., Alvarez, M. C. I., Bissinger, B. R. G., Sathian, M. B., Pignot, C. D., Haberhauer, A., Wu, D., Douat, C., et al. (2025) · JACS Au · doi:10.1021/jacsau.5c00692 · Cited by 4
Montaño, J. L., Tejus, V. R., Xu, V., Condon, A. C., Ecker, A. K., Langen, A., Leung, K. K., & Zaro, B. W. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.12.003 · Cited by 4
Ma, Y., Zhou, J., Guan, B., Zhang, X., Wang, J., Yan, J., Wang, K., & Ye, M. (2026) · Analytical Chemistry · doi:10.1021/acs.analchem.5c05384 · Cited by 3
Walker, J. C., Yan, K., & Derda, R. (2026) · Biochemistry · doi:10.1021/acs.biochem.5c00646 · Cited by 4
Quantitative Mapping of NHS Ester–Protein Reactivity Using Native Top-Down Mass Spectrometry
Bennett, J. L., Ramsay, O. B., Lutomski, C. A., Kirschbaum, C., & Robinson, C. V. (2026) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.5c00395 · Cited by 3
Covalent lysine targeting is coming of age
Livnah, E., & London, N. (2026) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2026.102671 · Cited by 4
Rudolph, J., Hoeflich, K. P., & Dar, A. C. (2026) · Nature Reviews Drug Discovery · doi:10.1038/s41573-026-01411-9 · Cited by 10
“…(NMR, crystallography) 75–78 , library screening with ATP-site masking (DEL, HTS, others) 79,80 , covalent and chemoproteomic mapping approaches 81,82 , biophysical approaches (HDX, LiP-MS, DSF, others) 83–85 , functional screening with disabled ATP binding 86 and virtual screening 87 , supported…”
An enantioselective covalent inhibitor of BAX confers cytoprotection in vivo
Shi, P., Melillo, B. N., McHenry, M. W., Camara, C. M., Yang, K., Njomen, E., Godes, M., Pazyra‐Murphy, M. F., Branch, M. R., Tesar, B. M., et al. (2026) · Nature Chemical Biology · doi:10.1038/s41589-026-02297-9 · Cited by 3
Self-citationLiang, W., Feng, X., Su, W., Zhong, L., Li, P., Wang, H., Li, T., Ruan, T., & Jiang, G. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.168266 · Cited by 3
NSPs: chromogenic linkers for fast, selective, and irreversible cysteine modification
Hua, Y., Zou, Z., Prescimone, A., Ward, T. R., Mayor, M., & Köhler, V. (2024) · Chemical Science · doi:10.1039/d4sc01710b · Cited by 3
A Chemoproteomic Approach to Monitor Native Iron–Sulfur Cluster Binding
Bak, D. W., & Weerapana, E. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-4043-2_16 · Cited by 3
Deciphering T Cell Immunometabolism with Activity-Based Protein Profiling
Borne, A. L., Huang, T., McCloud, R. L., Pachaiyappan, B., Bullock, T. N. J., & Hsu, K. (2018) · Current topics in microbiology and immunology · doi:10.1007/82_2018_124 · Cited by 3
“Given the ability of competitive ABPP to rapidly identify fragment leads (Backus et al. 2016; Hacker et al. 2017; Parker et al. 2017), future efforts will benefit from identification of new DGK fragment binders that can be optimized along with RF001 by linking, merging, and/or elaboration strategies to develop potent…”
BackgroundEnzymes engineered to trap reaction intermediates
Gulick, A. M. (2018) · Nature · doi:10.1038/d41586-018-07569-6 · Cited by 3
PES derivative PESA is a potent tool to globally profile cellular targets of PES
Yang, J., Liu, Z., Perrett, S., Zhang, H., & Pan, Z. (2022) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2022.128553 · Cited by 3
Computational and biophysical methods for the discovery and optimization of covalent drugs
Wang, G., Moitessier, N., & Mittermaier, A. (2023) · Chemical Communications · doi:10.1039/d3cc03285j · Cited by 6
Thermal proteome profiling unveils protein targets of deoxycholic acid in living neuronal cells
Luan, H., Li, X., Zhang, W., & Luan, T. (2023) · Advanced Biotechnology · doi:10.1007/s44307-023-00007-3 · Cited by 3
“Multiple proteomic technologies have been developed for the comprehensive analysis of entire proteomes, revealing hitherto unknown interactions between MBA and proteins (Backus et al. 2016; Mitchell et al. 2023; Prabhu et al. 2020).”
BackgroundSon, S.-Y., & Song, W. J. (2024) · Chemical Science · doi:10.1039/d3sc05448a · Cited by 3
“3 7 The creation and precise adjustment of novel protein – protein interactions (PPIs) can be employed for various potential applications, including proteome exploration, 8,9 biocatalytic cascade reaction, 10,11 allosteric control, and sensing.”
Sweetly profiling the cysteinome
Yang, J. H. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0348-9 · Cited by 3
What Do Reactive Fragments Actually Do in Cells?
Plettenburg, O. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201607914 · Cited by 3
Dhanaraj, P., Indiraleka, M., Selvakumar, P. M., & Enoch, I. V. M. V. (2020) · Materials Today Proceedings · doi:10.1016/j.matpr.2020.07.397 · Cited by 3
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
