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.
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
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?
Human CASP10 shares some substrate specificity with CASP8 and possibly contributes to extrinsic apoptosis in primary T cells.
“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]
Covalent inhibitors achieve high efficiency through forming covalent bonds with cysteine or other nucleophilic residues in the target protein.
“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]
Reactive cysteine residues on proteins have high nucleophilicity, which enables covalent binding with electrophilic small molecules.
“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 that study, more than 700 ligandable cysteines were identified and proteome-wide selectivity information was provided for each covalent fragment in the library.
“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]
Competitive isoTOP-ABPP was expanded to identify proteome-wide targets of a small covalent fragment library by competing acrylamide and chloroacetamide fragments against an iodoacetamide-alkyne probe.
“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]
This approach can rapidly identify compounds that target proteins of biological interest.
“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]
The covalent ligands and corresponding ligandable sites discovered with competitive isoTOP-ABPP helped elucidate the roles of caspase 8 and caspase 10 in extrinsic apoptosis in T cells.
“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]
The authors observed limited overlap of enantioprobe targets with proteins that demonstrated ligandability in previous chemical proteomic studies using cysteine- or lysine-reactive electrophilic fragments.
“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]
IsoTOP-ABPP is a well-validated method for covalent ligand target identification.
“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.
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 · see citing works
Berman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196 · see citing works
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 25,745 · see citing works
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 · see citing works
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 10,705 · see citing works
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 · see citing works
UniProt: a hub for protein information
The UniProt Consortium (2015) · Nucleic Acids Research · doi:10.1093/nar/gku989 · Cited by 5,106 · see citing works
Hopkins, A. L., & Groom, C. R. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd892 · Cited by 3,305 · see citing works
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 · see citing works
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 · see citing works
Phthalimide conjugation as a strategy for in vivo target protein degradation
Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760 · see citing works
Quantitative reactivity profiling predicts functional cysteines in proteomes
Weerapana, E., Wang, C., Simon, G. M., Richter, F., Khare, S., Dillon, M. B. D., Bachovchin, D. A., Mowen, K., Baker, D., & Cravatt, B. F. (2010) · Nature · doi:10.1038/nature09472 · Cited by 1,684 · see citing works
Self-citationBIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models
Li, D., Ambrogio, L., Shimamura, T., Kubo, S., Takahashi, M., Chirieac, L. R., Padera, R. F., Shapiro, G. I., Baum, A., Himmelsbach, F., et al. (2008) · Oncogene · doi:10.1038/onc.2008.109 · Cited by 1,447 · see citing works
Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4
Lu, J., Qian, Y., Altieri, M., Dong, H., Wang, J., Raina, K., Hines, J., Winkler, J. D., Crew, A. P., Coleman, K., et al. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2015.05.009 · Cited by 1,140 · see citing works
Selective inhibition of oncogenic KRAS output with small molecules targeting the inactive state
Patricelli, M. P., Janes, M. R., Li, L.-S., Hansen, R., Peters, U., Kessler, L. V., Chen, Y., Kucharski, J. M., Feng, J., Ely, T., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1105 · Cited by 759 · cited 1× · see citing works
“One fragment (11) marked in red showed notably lower reactivity in situ versus in vitro.”
BackgroundDeveloping Irreversible Inhibitors of the Protein Kinase Cysteinome
Liu, Q., Sabnis, Y. A., Zhao, Z., Zhang, T., Buhrlage, S. J., Jones, L. H., & Gray, N. S. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.12.006 · Cited by 662 · see citing works
Life and death in peripheral T cells
Krammer, P. H., Arnold, R., & Lavrik, I. N. (2007) · Nature reviews. Immunology · doi:10.1038/nri2115 · Cited by 652 · see citing works
Reduced surface: an efficient way to compute molecular surfaces.
Sanner, M. F., Olson, A. J., & Spehner, J.-C. (1996) · PubMed · doi:10.1002/(sici)1097-0282(199603)38:3%3c305::aid-bip4%3e3.0.co;2-y · Cited by 593 · see citing works
Self-citationSite-directed ligand discovery
Erlanson, D. A., Braisted, A. C., Raphael, D. R., Randal, M., Stroud, R. M., Gordon, E. M., & Wells, J. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.17.9367 · Cited by 466 · see citing works
Fragment-Based Approaches in Drug Discovery and Chemical Biology
Scott, D. E., Coyne, A. G., Hudson, S. A., & Abell, C. (2012) · Biochemistry · doi:10.1021/bi3005126 · Cited by 460 · see citing works
A road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors
Lanning, B. R., Whitby, L. R., Dix, M. M., Douhan, J., Gilbert, A. M., Hett, E. C., Johnson, T., Joslyn, C. M., Kath, J. C., Niessen, S., et al. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1582 · Cited by 361 · see citing works
Self-citationInhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins
Hoffstrom, B. G., Kaplan, A. R., Letso, R. R., Schmid, R. S., Turmel, G. J., Lo, D. C., & Stockwell, B. R. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.467 · Cited by 307 · see citing works
A chemoproteomic platform to quantitatively map targets of lipid-derived electrophiles
Wang, C., Weerapana, E., Blewett, M. M., & Cravatt, B. F. (2013) · Nature Methods · doi:10.1038/nmeth.2759 · Cited by 303 · see citing works
Self-citationTherapeutic Targeting of Oncogenic K‐Ras by a Covalent Catalytic Site Inhibitor
Lim, S. M., Westover, K. D., Ficarro, S. B., Harrison, R. A., Choi, H. G., Pacold, M. E., Carrasco, M., Hunter, J., Kim, N. D., Xie, T., et al. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307387 · Cited by 300 · see citing works
Weerapana, E., Speers, A. E., & Cravatt, B. F. (2007) · Nature Protocols · doi:10.1038/nprot.2007.194 · Cited by 276 · see citing works
Self-citationCovalent docking of large libraries for the discovery of chemical probes
London, N., Miller, R. M., Krishnan, S., Uchida, K., Irwin, J. J., Eidam, O., Gibold, L., Cimermančič, P., Bonnet, R., Shoichet, B. K., et al. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1666 · Cited by 274 · see citing works
Wissner, A., Overbeek, E., Reich, M. F., Floyd, M. B., Johnson, B. D., Mamuya, N. N., Rosfjord, E. C., Discafani, C. M., Davis, R. E., Shi, X., et al. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020241c · Cited by 270 · see citing works
Click-generated triazole ureas as ultrapotent in vivo–active serine hydrolase inhibitors
Adibekian, A., Martin, B. R., Wang, C., Hsu, K., Bachovchin, D. A., Niessen, S., Hoover, H. S., & Cravatt, B. F. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.579 · Cited by 244 · see citing works
Self-citationFragment screening to predict druggability (ligandability) and lead discovery success
Edfeldt, F., Folmer, R. H. A., & Breeze, A. L. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.02.002 · Cited by 201 · see citing works
GENETIC DISORDERS OF PROGRAMMED CELL DEATH IN THE IMMUNE SYSTEM
Bidère, N., Su, H. C., & Lenardo, M. J. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090513 · Cited by 197 · see citing works
Electrophilic Fragment-Based Design of Reversible Covalent Kinase Inhibitors
Miller, R. M., Paavilainen, V. O., Krishnan, S., Serafimova, I. M., & Taunton, J. (2013) · Journal of the American Chemical Society · doi:10.1021/ja401221b · Cited by 196 · see citing works
The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase
Inloes, J. M., Hsu, K., Dix, M. M., Viader, A., Masuda, K. R., Takei, T., Wood, M. R., & Cravatt, B. F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1413706111 · Cited by 175 · see citing works
Self-citationA Fragment-Based Method to Discover Irreversible Covalent Inhibitors of Cysteine Proteases
Kathman, S. G., Xu, Z., & Statsyuk, A. V. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500345q · Cited by 173 · cited 3× · see citing works
“With dual CASP8/10 (7) and CASP8-selective (63-R) ligands in hand, we next set out to investigate the biological functions of these proteases.”
BackgroundInfluentialJöst, C., Nitsche, C., Scholz, T., Roux, L., & Klein, C. D. P. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5006918 · Cited by 167 · see citing works
Held, J. M., Danielson, S. R., Behring, J. B., Atsriku, C., Britton, D. J., Puckett, R., Schilling, B., Campisi, J., Benz, C. C., & Gibson, B. W. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900643-mcp200 · Cited by 134 · see citing works
Imaging polysaccharides by atomic force microscopy
Kirby, A. R., Gunning, A. P., & Morris, V. J. (1998) · Biopolymers · doi:10.1002/(sici)1097-0282(199603)38:3 · Cited by 107 · see citing works
Activation and Specificity of Human Caspase-10
Wachmann, K., Pop, C., van Raam, B. J., Drąg, M., Mace, P. D., Snipas, S. J., Zmasek, C. M., Schwarzenbacher, R., Salvesen, G. S., & Riedl, S. J. (2010) · Biochemistry · doi:10.1021/bi100968m · Cited by 82 · see citing works
Cardoso, R., Love, R., Nilsson, C. L., Bergqvist, S., Nowlin, D., Yan, J., Liu, K. K. ‐., Zhu, J., Chen, P., Deng, Y., et al. (2012) · Protein Science · doi:10.1002/pro.2172 · Cited by 79 · see citing works
Kinetic Template‐Guided Tethering of Fragments
Nonoo, R. H., Armstrong, A., & Mann, D. J. (2012) · ChemMedChem · doi:10.1002/cmdc.201200404 · Cited by 47 · see citing works
Action at a Distance: Allostery and the Development of Drugs to Target Cancer Cell Metabolism
DeLaBarre, B., Hurov, J., Cianchetta, G., Murray, S., & Dang, L. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.08.007 · Cited by 44 · see citing works
Selective Detection and Inhibition of Active Caspase-3 in Cells with Optimized Peptides
Vickers, C. J., González-Páez, G. E., & Wolan, D. W. (2013) · Journal of the American Chemical Society · doi:10.1021/ja406399r · Cited by 43 · see citing works
Self-citationLafont, É., Milhas, D., Teissié, J., Therville, N., Andrieu‐Abadie, N., Levade, T., Benoist, H., & Ségui, B. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013638 · Cited by 21 · see citing works
Rostovtsev, V. V., Green, L. G., Fokin, V. V., & Sharpless, K. B. (2002) · Angewandte Chemie International Edition · doi:10.1002/1521-3773(20020715)41:14
Flagged first, then by citations
Research works printed but not linked: 1
- [34]Wang C Weerapana E Blewett MM Cravatt BF A chemoproteomic platform to quantitatively map targets of lipid-derived electrophiles Nat Meth 2014 11 79 85 PMC3901407 24292485
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
“Although human CASP10 shares some degree of substrate specificity with CASP8 [317] and possibly contributes to extrinsic apoptosis in primary T cells [318], rodents including mice and rats lack a functional Casp10 gene, and the precise role of this caspase in death receptor-driven apoptosis in humans and other CASP10-…”
BackgroundProteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery
Burslem, G. M., & Crews, C. M. (2020) · Cell · doi:10.1016/j.cell.2019.11.031 · Cited by 1,079 · see citing works
Kinase inhibitors: the road ahead
Ferguson, F. M., & Gray, N. S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.21 · Cited by 1,009 · see citing works
Opportunities and challenges in phenotypic drug discovery: an industry perspective
Moffat, J. G., Vincent, F., Lee, J. A., Eder, J., & Prunotto, M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.111 · Cited by 939 · see citing works
Advances in covalent drug discovery
Boike, L., Henning, N. J., & Nomura, D. K. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00542-z · Cited by 823 · see citing works
Gehringer, M., & Laufer, S. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01153 · Cited by 754 · see citing works
Expanding the medicinal chemistry synthetic toolbox
Boström, J., Brown, D. G., Young, R., & Keserű, G. (2018) · Nature reviews. Drug discovery · doi:10.1038/nrd.2018.116 · Cited by 498 · see citing works
Advancing targeted protein degradation for cancer therapy
Dale, B., Cheng, M., Park, K., Kanıskan, H. Ü., Xiong, Y., & Jin, J. J. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00365-x · Cited by 671 · see citing works
Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis
Wu, F.-H., Chi, Y., Jiang, Z., Xu, Y., Xie, L., Huang, F., Wan, D., Ni, J., Yuan, F., Wu, X., et al. (2020) · Nature · doi:10.1038/s41586-020-2032-3 · Cited by 583 · see citing works
A Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication
Piazza, I., Kochanowski, K., Cappelletti, V., Fuhrer, T., Noor, Ε., Sauer, U., & Picotti, P. (2018) · Cell · doi:10.1016/j.cell.2017.12.006 · Cited by 547 · see citing works
Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease
Douangamath, A., Fearon, D., Gehrtz, P., Krojer, T. J., Lukacik, P., Owen, C. D., Resnick, E., Strain-Damerell, C. M., Aimon, A., Ábrányi‐Balogh, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18709-w · Cited by 541 · see citing works
Selective covalent targeting of GPX4 using masked nitrile-oxide electrophiles
Eaton, J. K., Furst, L., Ruberto, R. A., Moosmayer, D., Hilpmann, A., Ryan, M. J., Zimmermann, K. C., Cai, L. L., Niehues, M., Badock, V., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0501-5 · Cited by 510 · see citing works
Global profiling of lysine reactivity and ligandability in the human proteome
Hacker, S. M., Backus, K. M., Lazear, M. R., Forli, S., Correia, B. E., & Cravatt, B. F. (2017) · Nature Chemistry · doi:10.1038/nchem.2826 · Cited by 485 · see citing works
Self-citationElectrophilic PROTACs that degrade nuclear proteins by engaging DCAF16
Zhang, X., Crowley, V. M., Wucherpfennig, T. G., Dix, M. M., & Cravatt, B. F. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0279-5 · Cited by 487 · see citing works
Self-citationAccelerating A uto D ock 4 with GPUs and Gradient-Based Local Search
Santos‐Martins, D., Solis-Vasquez, L., Tillack, A. F., Sanner, M. F., Koch, A., & Forli, S. (2021) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.0c01006 · Cited by 458 · see citing works
Self-citationLigand and Target Discovery by Fragment-Based Screening in Human Cells
Parker, C. G., Galmozzi, A., Wang, Y., Correia, B. E., Sasaki, K., Joslyn, C. M., Kim, A. S., Cavallaro, C. L., Lawrence, R. M., Johnson, S. R., et al. (2017) · Cell · doi:10.1016/j.cell.2016.12.029 · Cited by 439 · see citing works
Self-citationHarnessing the anti-cancer natural product nimbolide for targeted protein degradation
Spradlin, J. N., Hu, X., Ward, C. C., Brittain, S. M., Jones, M. D., Ou, L., To, M., Proudfoot, A., Ornelas, E., Woldegiorgis, M., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0304-8 · Cited by 432 · see citing works
“IsoTOP-ABPP studies were done as previously reported 12,14,15 .”
Advances in Targeting ‘Undruggable’ transcription Factors With Small Molecules
Henley, M. J., & Koehler, A. N. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00199-0 · Cited by 409 · see citing works
A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging
Xiao, H., Jedrychowski, M. P., Schweppe, D. K., Huttlin, E. L., Yu, Q., Heppner, D. E., Li, J., Long, J., Mills, E. L., Szpyt, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.012 · Cited by 399 · see citing works
Click Chemistry in Proteomic Investigations
Parker, C. G., & Pratt, M. R. (2020) · Cell · doi:10.1016/j.cell.2020.01.025 · Cited by 386 · see citing works
An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells
Vinogradova, E. V., Zhang, X., Remillard, D., Lazar, D. C., Suciu, R. M., Wang, Y., Bianco, G., Yamashita, Y., Crowley, V. M., Schafroth, M. A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.001 · Cited by 351 · see citing works
Self-citationTamura, T., & Hamachi, I. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b11747 · Cited by 339 · see citing works
Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development
Donovan, K. A., Ferguson, F. M., Bushman, J. W., Eleuteri, N. A., Bhunia, D., Ryu, S., Tan, L., Shi, K., Yue, H., Liu, X., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.038 · Cited by 359 · see citing works
Structure-based design of targeted covalent inhibitors
Lonsdale, R., & Ward, R. A. (2018) · Chemical Society Reviews · doi:10.1039/c7cs00220c · Cited by 344 · see citing works
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 · see citing works
Self-citationThe 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 355 · see citing works
Deubiquitinase-targeting chimeras for targeted protein stabilization
Henning, N. J., Boike, L., Spradlin, J. N., Ward, C. C., Liu, G., Zhang, E., Belcher, B. P., Brittain, S. M., Hesse, M. J., Dovala, D., et al. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-00971-2 · Cited by 344 · see citing works
Advances in covalent kinase inhibitors
Abdeldayem, A., Raouf, Y. S., Constantinescu, S. N., Moriggl, R., & Gunning, P. T. (2020) · Chemical Society Reviews · doi:10.1039/c9cs00720b · Cited by 332 · see citing works
Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening
Resnick, E., Bradley, A., Gan, J., Douangamath, A., Krojer, T., Sethi, R., Geurink, P. P., Aimon, A., Amitai, G., Bellini, D., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b02822 · Cited by 335 · see citing works
Ward, C. C., Kleinman, J. I., Brittain, S. M., Lee, P. S., Chung, C. Y. S., Kim, K., Petri, Y., Thomas, J. R., Tallarico, J. A., McKenna, J. M., et al. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.8b01083 · Cited by 336 · see citing works
S-glycosylation-based cysteine profiling reveals regulation of glycolysis by itaconate
Qin, W., Qin, K., Zhang, Y., Jia, W., Chen, Y., Cheng, B., Peng, L., Chen, N., Liu, Y., Zhou, W., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0323-5 · Cited by 317 · see citing works
Chemistries of bifunctional PROTAC degraders
Cao, C., He, M., Wang, L., He, Y., & Rao, Y. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00220e · Cited by 313 · see citing works
Disulfidptosis: disulfide stress–induced cell death
Liu, X., Zhuang, L., & Gan, B. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.07.009 · Cited by 317 · see citing works
Target and tissue selectivity of PROTAC degraders
Guenette, R. G., Yang, S. W., Min, J., Pei, B., & Potts, P. R. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00200k · Cited by 324 · see citing works
Mortenson, D. E., Brighty, G. J., Plate, L., Bare, G. A. L., Chen, W., Li, S., Wang, H., Cravatt, B. F., Forli, S., Powers, E. T., et al. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b08366 · Cited by 301 · see citing works
Self-citationChemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer
Bar-Peled, L., Kemper, E. K., Suciu, R. M., Vinogradova, E. V., Backus, K. M., Horning, B. D., Paul, T. A., Ichu, T.-A., Svensson, R. U., Olucha, J., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.051 · Cited by 262 · see citing works
“…http://dx.doi.org/10.1016/j.cell.2017.08.051 of scout fragments found previously to show broad reactivity with cysteines across the human proteome (Backus et al., 2016), we simplified the search for ligandable cysteines in NSCLC lines, and we anticipate that this approach should facilitate the…”
InfluentialSelf-citationConcepts and Core Principles of Fragment-Based Drug Design
Kirsch, P., Hartman, A. M., Hirsch, A. K. H., & Empting, M. (2019) · Molecules · doi:10.3390/molecules24234309 · Cited by 243 · see citing works
“have described the use of a chemical proteomic method in order to perform fragment-based ligand discovery in native biological systems [21].”
MethodA proteome-wide atlas of lysine-reactive chemistry
Abbasov, M. E., Kavanagh, M. E., Ichu, T.-A., Lazear, M. R., Tao, Y., Crowley, V. M., Ende, C. W. A., Hacker, S. M., Ho, J. S., Dix, M. M., et al. (2021) · Nature Chemistry · doi:10.1038/s41557-021-00765-4 · Cited by 242 · see citing works
Self-citationThe Cysteinome of Protein Kinases as a Target in Drug Development
Chaikuad, A., Koch, P., Laufer, S., & Knapp, S. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201707875 · Cited by 237 · see citing works
Goodsell, D. S., Sanner, M. F., Olson, A. J., & Forli, S. (2020) · Protein Science · doi:10.1002/pro.3934 · Cited by 239 · see citing works
Self-citationGao, J., Hou, B., Zhu, Q., Yang, L., Jiang, X., Zou, Z., Li, X., Xu, T., Zheng, M., Chen, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32050-4 · Cited by 226 · see citing works
Targeted protein degradation for cancer therapy
Hinterndorfer, M., Spiteri, V. A., Ciulli, A., & Winter, G. E. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00817-8 · Cited by 245 · see citing works
“Modern chemoproteomics approaches allow for high-throughput screening directly in cells, providing opportunities for the discovery of novel binders 261 .”
Recent Developments in PROTAC‐Mediated Protein Degradation: From Bench to Clinic
Hu, Z., & Crews, C. M. (2022) · ChemBioChem · doi:10.1002/cbic.202100270 · Cited by 231 · see citing works
Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases
Guo, C., Chang, F., Wyche, T. P., Backus, K. M., Acker, T. M., Funabashi, M., Taketani, M., Donia, M. S., Nayfach, S., Pollard, K. S., et al. (2017) · Cell · doi:10.1016/j.cell.2016.12.021 · Cited by 215 · see citing works
“Scientific) coupled to an Agilent 1200- series quaternary pump and searched and analyzed as has been reported previously (Backus et al., 2016).”
MethodSelf-citationDiscovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications
Henning, N. J., Manford, A. G., Spradlin, J. N., Brittain, S. M., Zhang, E., McKenna, J. M., Tallarico, J. A., Schirle, M., Rape, M., & Nomura, D. K. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.1c03980 · Cited by 221 · see citing works
Recent Advances in Design of Fluorescence-Based Assays for High-Throughput Screening
Fang, X., Zheng, Y., Duan, Y., Liu, Y., & Zhong, W. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b05303 · Cited by 211 · see citing works
Emerging and Re-emerging Warheads for Targeted Covalent Inhibitors: An Update
Hillebrand, L., Liang, X. J., Serafim, R. A. M., & Gehringer, M. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01825 · Cited by 212 · see citing works
Progress with covalent small-molecule kinase inhibitors
Zhao, Z., & Bourne, P. E. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.01.035 · Cited by 200 · see citing works
Application of Fragment-Based Drug Discovery to Versatile Targets
Li, Q. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00180 · Cited by 203 · see citing works
Covalent targeted radioligands potentiate radionuclide therapy
Cui, X., Li, Z., Kong, Z., Liu, Y., Meng, H., Wen, Z., Wang, C., Chen, J., Xu, M., Li, Y., et al. (2024) · Nature · doi:10.1038/s41586-024-07461-6 · Cited by 206 · see citing works
Cecchini, C., Pannilunghi, S., Tardy, S., & Scapozza, L. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.672267 · Cited by 198 · see citing works
“A library of electrophilic covalent fragments (called “scouts”) targeting several “undruggable” proteins was built in Cravatt’s lab to help discover electrophilic E3 ligands in cell-lysates (Backus et al., 2016; Zhang et al., 2019b).”
BackgroundDCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras
Zhang, X., Luukkonen, L. M., Eissler, C. L., Crowley, V. M., Yamashita, Y., Schafroth, M. A., Kikuchi, S., Weinstein, D. S., Symons, K. T., Nordin, B. E., et al. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c00990 · Cited by 199 · see citing works
Self-citationRational Chemical Design of Molecular Glue Degraders
Toriki, E. S., Papatzimas, J. W., Nishikawa, K., Dovala, D., Frank, A. O., Hesse, M. J., Danková, D., Song, J.-G., Bruce-Smythe, M., Struble, H., et al. (2023) · ACS Central Science · doi:10.1021/acscentsci.2c01317 · Cited by 196 · see citing works
Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells
Blewett, M. M., Xie, J., Zaro, B. W., Backus, K. M., Altman, A., Teijaro, J. R., & Cravatt, B. F. (2016) · Science Signaling · doi:10.1126/scisignal.aaf7694 · Cited by 194 · see citing works
Self-citationPROTACs to address the challenges facing small molecule inhibitors
Martín-Acosta, P., & Xiao, X. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112993 · Cited by 186 · see citing works
Reactive-cysteine profiling for drug discovery
Maurais, A. J., & Weerapana, E. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.02.010 · Cited by 167 · see citing works
Keedy, D. A., Hill, Z. B., Biel, J. T., Kang, E., Rettenmaier, T. J., Brandão-Neto, J., Pearce, N. M., von Delft, F., Wells, J. A., & Fraser, J. S. (2018) · eLife · doi:10.7554/elife.36307 · Cited by 185 · see citing works
Recent Advances in Selective and Irreversible Covalent Ligand Development and Validation
Zhang, T., Hatcher, J. M., Teng, M., Gray, N. S., & Kostic, M. (2019) · Cell Chemical Biology · doi:10.1016/j.chembiol.2019.09.012 · Cited by 178 · see citing works
“conducted a competitive isoTOP-ABPP based screen of a library containing approximately 60 electrophilic fragments in two human cell lines to profile in-cell reactivity (Backus et al., 2016).”
MethodPiazza, I., Beaton, N., Bruderer, R., Knobloch, T., Barbisan, C., Chandat, L., Sudau, A., Siepe, I., Rinner, O., de Souza, N., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18071-x · Cited by 183 · see citing works
Luo, M., Spradlin, J. N., Boike, L., Tong, B., Brittain, S. M., McKenna, J. M., Tallarico, J. A., Schirle, M., Maimone, T. J., & Nomura, D. K. (2021) · Cell Chemical Biology · doi:10.1016/j.chembiol.2021.01.005 · Cited by 186 · see citing works
Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs
Wang, Y., Dix, M. M., Bianco, G., Remsberg, J. R., Lee, H.-Y., Kalocsay, M., Gygi, S. P., Forli, S., Vite, G., Lawrence, R. M., et al. (2019) · Nature Chemistry · doi:10.1038/s41557-019-0351-5 · Cited by 179 · see citing works
Self-citationCovalent Targeting of the Vacuolar H+-ATPase Activates Autophagy Via mTORC1 Inhibition
Chung, C., Shin, H. R., Berdan, C. A., Ford, B., Ward, C. C., Olzmann, J. A., Zoncu, R., & Nomura, D. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0308-4 · Cited by 173 · see citing works
E3 ligase ligand chemistries: from building blocks to protein degraders
Sosič, I., Bricelj, A., & Steinebach, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00148a · Cited by 173 · see citing works
Reimagining Druggability Using Chemoproteomic Platforms
Spradlin, J. N., Zhang, E., & Nomura, D. K. (2021) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00065 · Cited by 176 · see citing works
How We Think about Targeting RNA with Small Molecules
Costales, M. G., Childs‐Disney, J. L., Haniff, H. S., & Disney, M. D. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01927 · Cited by 164 · see citing works
Targeting Metabolic–Redox Circuits for Cancer Therapy
Wang, K., Jiang, J., Lei, Y., Zhou, S., Wei, Y., & Huang, C. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.01.001 · Cited by 162 · see citing works
Cysteine Oxidation in Proteins: Structure, Biophysics, and Simulation
Ruiz, D. G., Sandoval‐Pérez, A., Rangarajan, A. V., Gunderson, E. L., & Jacobson, M. P. (2022) · Biochemistry · doi:10.1021/acs.biochem.2c00349 · Cited by 161 · see citing works
2H-Azirine-Based Reagents for Chemoselective Bioconjugation at Carboxyl Residues Inside Live Cells
Ma, N., Hu, J., Zhang, Z., Liu, W., Huang, M., Fan, Y., Yin, X., Wang, J., Ding, K., Ye, W., et al. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.9b12116 · Cited by 160 · see citing works
Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo
Dubiella, C., Pinch, B. J., Koikawa, K., Zaidman, D., Poon, E., Manz, T. D., Nabet, B., He, S., Resnick, E., Rogel, A., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00786-7 · Cited by 161 · see citing works
NHS-Esters As Versatile Reactivity-Based Probes for Mapping Proteome-Wide Ligandable Hotspots
Ward, C. C., Kleinman, J. I., & Nomura, D. K. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00125 · Cited by 158 · see citing works
Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC
Boike, L., Cioffi, A. G., Majewski, F. C., Co, J., Henning, N. J., Jones, M. D., Liu, G., McKenna, J. M., Tallarico, J. A., Schirle, M., et al. (2021) · Cell Chemical Biology · doi:10.1016/j.chembiol.2020.09.001 · Cited by 154 · see citing works
The role of reversible and irreversible covalent chemistry in targeted protein degradation
Kiely‐Collins, H., Winter, G. E., & Bernardes, G. J. L. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.03.005 · Cited by 156 · see citing works
Comparative Evaluation of Covalent Docking Tools
Scarpino, A., Ferenczy, G. G., & Keserű, G. M. (2018) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.8b00228 · Cited by 152 · see citing works
Recent advances in identifying protein targets in drug discovery
Ha, J., Park, H., Park, J., & Park, S. B. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.12.001 · Cited by 158 · see citing works
Discovering the landscape of protein modifications
Keenan, E. K., Zachman, D. K., & Hirschey, M. D. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.015 · Cited by 154 · see citing works
Template-assisted covalent modification underlies activity of covalent molecular glues
Li, Y.-D., Ma, M. W., Hassan, M. M., Hunkeler, M., Teng, M., Puvar, K., Rutter, J. C., Lumpkin, R. J., Sandoval, B., Jin, C. Y., et al. (2024) · Nature Chemical Biology · doi:10.1038/s41589-024-01668-4 · Cited by 147 · see citing works
“More broadly, it is likely that many sites observed in chemo-proteomics covalent fragment screens 34,35 , and especially those observed in unstructured regions, may be the result of a similar template-assisted mechanism in which the primary binding energy is derived from a binding partner.”
Tokunaga, K., Sato, M., Kuwata, K., Miura, C., Fuchida, H., Matsunaga, N., Koyanagi, S., Ohdo, S., Shindo, N., & Ojida, A. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c07490 · Cited by 145 · see citing works
Assessing Lysine and Cysteine Reactivities for Designing Targeted Covalent Kinase Inhibitors
Liu, R., Yue, Z., Tsai, C.-C., & Shen, J. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b13248 · Cited by 137 · see citing works
Covalent inhibitors: an opportunity for rational target selectivity
Lagoutte, R., Patouret, R., & Winssinger, N. (2017) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2017.05.008 · Cited by 138 · see citing works
Selective and reversible modification of kinase cysteines with chlorofluoroacetamides
Shindo, N., Fuchida, H., Sato, M., Watari, K., Shibata, T., Kuwata, K., Miura, C., Okamoto, K., Hatsuyama, Y., Tokunaga, K., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-018-0204-3 · Cited by 137 · see citing works
Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications
Mertens, R. T., Gukathasan, S., Arojojoye, A. S., Olelewe, C., & Awuah, S. G. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00649 · Cited by 140 · see citing works
Fragment-based covalent ligand discovery
Lu, W., Kostic, M., Zhang, T., Che, J., Patricelli, M. P., Jones, L. H., Chouchani, E. T., & Gray, N. S. (2021) · RSC Chemical Biology · doi:10.1039/d0cb00222d · Cited by 136 · see citing works
Chemical Tools for Endogenous Protein Labeling and Profiling
Shiraiwa, K., Cheng, R., Nonaka, H., Tamura, T., & Hamachi, I. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.06.016 · Cited by 132 · see citing works
Ligandability of E3 Ligases for Targeted Protein Degradation Applications
Belcher, B. P., Ward, C. C., & Nomura, D. K. (2023) · Biochemistry · doi:10.1021/acs.biochem.1c00464 · Cited by 132 · see citing works
A road map for prioritizing warheads for cysteine targeting covalent inhibitors
Ábrányi‐Balogh, P., Petri, L., Imre, T., Szijj, P. A., Scarpino, A., Hrast, M., Mitrović, A., Fonović, U. P., Németh, K., Barreteau, H., et al. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.10.010 · Cited by 132 · see citing works
Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase
Baltgalvis, K. A., Lamb, K. N., Symons, K. T., Wu, C.-C., Hoffman, M. A., Snead, A. N., Song, X., Glaza, T., Kikuchi, S., Green, J. C., et al. (2024) · Nature · doi:10.1038/s41586-024-07318-y · Cited by 130 · see citing works
Protein–protein interactions: scoring schemes and binding affinity
Gromiha, M. M., Yugandhar, K., & Jemimah, S. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.10.016 · Cited by 127 · see citing works
Determining Cysteines Available for Covalent Inhibition Across the Human Kinome
Zhao, Z., Liu, Q., Bliven, S. E., Xie, L., & Bourne, P. E. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01815 · Cited by 126 · see citing works
Fragment-Based Drug Discovery: Advancing Fragments in the Absence of Crystal Structures
Erlanson, D. A., Davis, B. J., & Jahnke, W. (2018) · Cell chemical biology · doi:10.1016/j.chembiol.2018.10.001 · Cited by 126 · see citing works
Johansson, H., Tsai, Y. I., Fantom, K. G. M., Chung, C., Kuemper, S., Martino, L., Thomas, D. A., Eberl, H. C., Muelbaier, M., House, D., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b13193 · Cited by 125 · see citing works
Diacylfuroxans Are Masked Nitrile Oxides That Inhibit GPX4 Covalently
Eaton, J. K., Ruberto, R. A., Kramm, A., Viswanathan, V. S., & Schreiber, S. L. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b10769 · Cited by 129 · see citing works
10 Years Into the Resurgence of Covalent Drugs
Vita, E. D. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2020-0236 · Cited by 125 · see citing works
“The concept of targeted reactivity has been slowly developed on the basis of novel experimental evidence and the advent of whole proteomic analytical techniques, showing that indeed covalent inhibition is not necessarily associated with promiscuity [10,11].”
BackgroundBach, K., Beerkens, B. L. H., Zanon, P. R. A., & Hacker, S. M. (2020) · ACS Central Science · doi:10.1021/acscentsci.9b01268 · Cited by 127 · see citing works
Diverse Redoxome Reactivity Profiles of Carbon Nucleophiles
Gupta, V., Yang, J. H., Liebler, D. C., & Carroll, K. S. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b01791 · Cited by 126 · see citing works
Dalton, S. E., Dittus, L., Thomas, D. A., Convery, M. A., Nunes, J., Bush, J. T., Evans, J. P., Werner, T., Bantscheff, M., Murphy, J. A., et al. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b08979 · Cited by 126 · see citing works
Tunable Heteroaromatic Sulfones Enhance in-Cell Cysteine Profiling
Motiwala, H. F., Kuo, Y.-H., Stinger, B. L., Palfey, B. A., & Martin, B. R. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b08831 · Cited by 125 · see citing works
Covalent Ligand Discovery against Druggable Hotspots Targeted by Anti-cancer Natural Products
Grossman, E. A., Ward, C. C., Spradlin, J. N., Bateman, L. A., Huffman, T. R., Miyamoto, D. K., Kleinman, J. I., & Nomura, D. K. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.08.013 · Cited by 124 · see citing works
Manumycin polyketides act as molecular glues between UBR7 and P53
Isobe, Y., Okumura, M., McGregor, L. M., Brittain, S. M., Jones, M. D., Liang, X., White, R., Forrester, W., McKenna, J. M., Tallarico, J. A., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0557-2 · Cited by 124 · see citing works
A chemoproteomic portrait of the oncometabolite fumarate
Kulkarni, R. A., Bak, D. W., Wei, D., Bergholtz, S. E., Briney, C. A., Shrimp, J. H., Alpsoy, A., Thorpe, A. L., Bavari, A. E., Crooks, D. R., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-018-0217-y · Cited by 121 · see citing works
Zanon, P. R. A., Lewald, L., & Hacker, S. M. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201912075 · Cited by 114 · see citing works
- 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 · 2012: 1
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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
