The DOI matches its Crossref record; 106 of the 111 references it cites were found in a registry or an index.
Haven't got a glue: Protein surface variation for the design of molecular glue degraders
Open accessAbstract
Molecular glue degraders are small, drug-like compounds that induce interactions between an E3 ubiquitin ligase and a target, which result in ubiquitination and subsequent degradation of the recruited protein. In recent years, serendipitous discoveries revealed that some preclinical and clinical compounds already work as molecular glue degraders, with many more postulated to destabilize their targets through indirect or yet unresolved mechanisms. Here we review strategies by which E3 ubiquitin ligases can be reprogrammed by monovalent degraders, with a focus on molecular glues hijacking cullin-RING ubiquitin ligases. We argue that such drugs exploit the intrinsic property of proteins to form higher-order assemblies, a phenomenon previously seen with disease-causing sequence variations. Modifications of the protein surface by a bound small molecule can change the interactome of the target protein. By inducing interactions between a ligase and a substrate, molecular glue degraders offer an exciting path for the development of novel therapeutics.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“Currently, there is no well-established computational framework to predict and evaluate compound-induced PPIs.251”
From Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence (2023) · cites this paper as [251]
Citations
Cites
Inference of Macromolecular Assemblies from Crystalline State
Krissinel, E., & Henrick, K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.05.022 · Cited by 10,007
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116
Sakamoto, K. M., Kim, K. B., Kumagai, A., Mercurio, F., Crews, C. M., & Deshaies, R. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141230798 · Cited by 2,609
Cyclin is degraded by the ubiquitin pathway
Glotzer, M., Murray, A. W., & Kirschner, M. W. (1991) · Nature · doi:10.1038/349132a0 · Cited by 2,359
Identification of a Primary Target of Thalidomide Teratogenicity
Ito, T., Ando, H., Suzuki, T., Ogura, T., Hotta, K., Imamura, Y., Yamaguchi, Y., & Handa, H. (2010) · Science · doi:10.1126/science.1177319 · Cited by 2,136
The mechanism of action of cyclosporin A and FK506
Schreiber, S. L., & Crabtree, G. R. (1992) · Immunology Today · doi:10.1016/0167-5699(92)90111-j · Cited by 2,127
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
Soucy, T. A., Smith, P. G., Milhollen, M. A., Berger, A. J., Gavin, J. M., Adhikari, S., Brownell, J. E., Burke, K. E., Cardin, D. P., Critchley, S., et al. (2009) · Nature · doi:10.1038/nature07884 · Cited by 1,990
Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
Krönke, J., Udeshi, N. D., Narla, A., Grauman, P., Hurst, S. N., McConkey, M., Svinkina, T., Heckl, D., Comer, E., Li, X., et al. (2014) · Science · doi:10.1126/science.1244851 · Cited by 1,879
Einfluss der Configuration auf die Wirkung der Enzyme
Fischer, E. (1894) · Berichte der deutschen chemischen Gesellschaft · doi:10.1002/cber.18940270364 · Cited by 1,841
Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods
Du, X., Li, Y., Xia, Y.-L., Ai, S.-M., Liang, J., Sang, P., Ji, X., & Liu, S.-Q. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020144 · Cited by 1,765
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
Mechanism of auxin perception by the TIR1 ubiquitin ligase
Tan, X., Calderon-Villalobos, L. I. A., Sharon, M., Zheng, C., Robinson, C. V., Estelle, M., & Zheng, N. (2007) · Nature · doi:10.1038/nature05731 · Cited by 1,688
An auxin-based degron system for the rapid depletion of proteins in nonplant cells
Nishimura, K., Fukagawa, T., Takisawa, H., Kakimoto, T., & Kanemaki, M. (2009) · Nature Methods · doi:10.1038/nmeth.1401 · Cited by 1,663
The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins
Lu, G., Middleton, R. E., Sun, H., Naniong, M., Ott, C. J., Mitsiades, C. S., Wong, K.-K., Bradner, J. E., & Kaelin, W. G. (2014) · Science · doi:10.1126/science.1244917 · Cited by 1,583
Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., & Snyder, S. H. (1994) · Cell · doi:10.1016/0092-8674(94)90570-3 · Cited by 1,509
Jasmonate perception by inositol-phosphate-potentiated COI1–JAZ co-receptor
Sheard, L. B., Tan, X., Mao, H., Withers, J., Ben-Nissan, G., Hinds, T. R., Kobayashi, Y., Hsu, F.-F., Sharon, M., Browse, J., et al. (2010) · Nature · doi:10.1038/nature09430 · Cited by 1,497
Catalytic in vivo protein knockdown by small-molecule PROTACs
Bondeson, D. P., Mares, A., Smith, I. E. D., Ko, E., Campos, S., Miah, A. H., Mulholland, K. E., Routly, N., Buckley, D. L., Gustafson, J. L., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1858 · Cited by 1,356
Structural basis of PROTAC cooperative recognition for selective protein degradation
Gadd, M. S., Testa, A., Lucas, X., Chan, K.-H., Chen, W., Lamont, D. J., Zengerle, M., & Ciulli, A. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2329 · Cited by 1,242
Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide
Fischer, E. S., Böhm, K., Lydeard, J. R., Yang, H., Stadler, M. B., Cavadini, S., Nagel, J., Serluca, F., Acker, V., Lingaraju, G. M., et al. (2014) · Nature · doi:10.1038/nature13527 · Cited by 1,141
Self-citationSmall molecules, big targets: drug discovery faces the protein–protein interaction challenge
Scott, D. E., Bayly, A. R., Abell, C., & Skidmore, J. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.29 · Cited by 1,137
Proteolysis-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
Thalidomide-induced Teratogenesis: History and Mechanisms
Vargesson, N. (2015) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.21096 · Cited by 912
Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells
Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., & Abraham, R. T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.2.815 · Cited by 887
Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS
Krönke, J., Fink, E. C., Hollenbach, P. W., MacBeth, K. J., Hurst, S. N., Udeshi, N. D., Chamberlain, P. P., Mani, D. R., Man, H. W., Gandhi, A. K., et al. (2015) · Nature · doi:10.1038/nature14610 · Cited by 863
Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15
Han, T., Goralski, M., Gaskill, N., Capota, E., Kim, J., Ting, T. C., Xie, Y., Williams, N. S., & Nijhawan, D. (2017) · Science · doi:10.1126/science.aal3755 · Cited by 762
A Review on Applications of Computational Methods in Drug Screening and Design
Lin, X., Li, X., & Lin, X. (2020) · Molecules · doi:10.3390/molecules25061375 · Cited by 718
A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase
Matyskiela, M. E., Lu, G., Ito, T., Pagarigan, B., Lu, C.-C., Miller, K., Fang, W., Wang, N.-Y., Nguyen, D., Houston, J., et al. (2016) · Nature · doi:10.1038/nature18611 · Cited by 701
Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery
Angers, S., Li, T., Yi, X., MacCoss, M. J., Moon, R. T., & Zheng, N. (2006) · Nature · doi:10.1038/nature05175 · Cited by 674
Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase
Petzold, G., Fischer, E. S., & Thomä, N. H. (2016) · Nature · doi:10.1038/nature16979 · Cited by 620
Self-citationGandhi, A. K., Kang, J., Havens, C. G., Conklin, T., Ning, Y., Wu, L., Ito, T., Ando, H., Waldman, M. F., Thakurta, A., et al. (2014) · British Journal of Haematology · doi:10.1111/bjh.12708 · Cited by 619
Plasticity in binding confers selectivity in ligand-induced protein degradation
Nowak, R. P., DeAngelo, S. L., Buckley, D., He, Z., Donovan, K. A., An, J., Safaee, N., Jedrychowski, M. P., Ponthier, C. M., Ishoey, M., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0055-y · Cited by 615
Structure of a β-TrCP1-Skp1-β-Catenin Complex
Wu, G., Xu, G., Schulman, B. A., Jeffrey, P. D., Harper, J. W., & Pavletich, N. P. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00234-x · Cited by 612
UV-Induced Ubiquitylation of XPC Protein Mediated by UV-DDB-Ubiquitin Ligase Complex
Sugasawa, K., Okuda, Y., Saijo, M., Nishi, R., Matsuda, N., Chu, G., Mori, T., Iwai, S., Tanaka, K., Tanaka, K., et al. (2005) · Cell · doi:10.1016/j.cell.2005.02.035 · Cited by 576
BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design
Farnaby, W., Koegl, M., Roy, M. J., Whitworth, C., Diers, E., Trainor, N., Zollman, D., Steurer, S., Karolyi-Oezguer, J., Riedmueller, C., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0294-6 · Cited by 562
Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN
Sievers, Q. L., Petzold, G., Bunker, R. D., Renneville, A., Słabicki, M., Liddicoat, B. J., Abdulrahman, W., Mikkelsen, T., Ebert, B. L., & Thomä, N. H. (2018) · Science · doi:10.1126/science.aat0572 · Cited by 537
Self-citationChamberlain, P. P., Lopez-Girona, A., Miller, K., Carmel, G., Pagarigan, B., Chie-Leon, B., Rychak, E., Corral, L. G., Ren, Y. J., Wang, M., et al. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2874 · Cited by 531
Donovan, K. A., An, J., Nowak, R. P., Yuan, J. C., Fink, E. C., Berry, B. C., Ebert, B. L., & Fischer, E. S. (2018) · eLife · doi:10.7554/elife.38430 · Cited by 509
The Molecular Basis of CRL4DDB2/CSA Ubiquitin Ligase Architecture, Targeting, and Activation
Fischer, E. S., Scrima, A., Böhm, K., Matsumoto, S., Lingaraju, G. M., Faty, M., Yasuda, T., Cavadini, S., Wakasugi, M., Hanaoka, F., et al. (2011) · Cell · doi:10.1016/j.cell.2011.10.035 · Cited by 460
Self-citationThe CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K
Słabicki, M., Kozicka, Z., Petzold, G., Li, Y.-D., Manojkumar, M., Bunker, R. D., Donovan, K. A., Sievers, Q. L., Koeppel, J., Suchyta, D., et al. (2020) · Nature · doi:10.1038/s41586-020-2374-x · Cited by 433
Self-citationSelective degradation of splicing factor CAPERα by anticancer sulfonamides
Uehara, T., Minoshima, Y., Sagane, K., Sugi, N. H., Mitsuhashi, K. O., Yamamoto, N., Kamiyama, H., Takahashi, K., Kotake, Y., Uesugi, M., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2363 · Cited by 396
Rational discovery of molecular glue degraders via scalable chemical profiling
Mayor-Ruiz, C., Bauer, S., Brand, M., Kozicka, Z., Siklos, M., Imrichova, H., Kaltheuner, I. H., Hahn, E., Seiler, K., Koren, A., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0594-x · Cited by 369
Self-citationMapping 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
Therapeutic Targeting of CDK12/CDK13 in Triple-Negative Breast Cancer
Quereda, V., Bayle, S., Vena, F., Frydman, S. M., Monastyrskyi, A., Roush, W. R., & Duckett, D. R. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.09.004 · Cited by 352
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor
Renault, L., Guibert, B., & Cherfils, J. (2003) · Nature · doi:10.1038/nature02197 · Cited by 326
Discovery of Novel Antitumor Sulfonamides Targeting G1 Phase of the Cell Cycle
Owa, T., Yoshino, H., Okauchi, T., Yoshimatsu, K., Ozawa, Y., Sugi, N. H., Nagasu, T., Koyanagi, N., & Kitoh, K. (1999) · Journal of Medicinal Chemistry · doi:10.1021/jm9902638 · Cited by 322
A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos
Matyskiela, M. E., Zhang, W., Man, H.-W., Muller, G., Khambatta, G., Baculi, F., Hickman, M., LeBrun, L., Pagarigan, B., Carmel, G., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01921 · Cited by 309
Small-molecule-induced polymerization triggers degradation of BCL6
Słabicki, M., Yoon, H., Koeppel, J., Nitsch, L., Roy Burman, S. S., Di Genua, C., Donovan, K. A., Sperling, A. S., Hunkeler, M., Tsai, J. M., et al. (2020) · Nature · doi:10.1038/s41586-020-2925-1 · Cited by 270
Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex
Bussiere, D. E., Xie, L., Srinivas, H., Shu, W., Burke, A., Be, C., Zhao, J., Godbole, A., King, D., Karki, R. G., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-019-0411-6 · Cited by 257
Proteins evolve on the edge of supramolecular self-assembly
Garcia-Seisdedos, H., Empereur-Mot, C., Elad, N., & Levy, E. D. (2017) · Nature · doi:10.1038/nature23320 · Cited by 253
Mossessova, E., Corpina, R. A., & Goldberg, J. D. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00475-1 · Cited by 244
Protein interaction networks revealed by proteome coevolution
Cong, Q., Anishchenko, I., Ovchinnikov, S., & Baker, D. (2019) · Science · doi:10.1126/science.aaw6718 · Cited by 241
Structural Basis for an Unexpected Mode of SERM-Mediated ER Antagonism
Wu, Y.-L., Yang, X., Ren, Z. M., McDonnell, D. P., Norris, J. D., Willson, T. M., & Greene, G. L. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.04.014 · Cited by 236
Scrima, A., Fischer, E. S., Iwai, S., Gut, H., & Thomä, N. H. (2011) · Worldwide Protein Data Bank · doi:10.2210/pdb4a08/pdb · Cited by 233
Self-citationSurka, C., Jin, L., Mbong, N., Lu, C.-C., Jang, I. S., Rychak, E., Mendy, D., Clayton, T., Tindall, E., Hsu, C., et al. (2021) · Blood · doi:10.1182/blood.2020008676 · Cited by 229
Structural assembly of cullin-RING ubiquitin ligase complexes
Zimmerman, E. S., Schulman, B. A., & Zheng, N. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.08.010 · Cited by 227
Li, T., Robert, E. I., Breugel, P. C. V., Strubin, M., & Zheng, N. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1719 · Cited by 223
Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15
Faust, T. B., Yoon, H., Nowak, R. P., Donovan, K. A., Li, Z., Cai, Q., Eleuteri, N. A., Zhang, T., Gray, N. S., & Fischer, E. S. (2020) · Nature Chemical Biology · doi:10.1038/s41589-019-0378-3 · Cited by 218
Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction
Simonetta, K. R., Taygerly, J., Boyle, K., Basham, S. E., Padovani, C., Lou, Y., Cummins, T. J., Yung, S. L., von Soly, S. K., Kayser, F., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09358-9 · Cited by 217
Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation
Lv, L., Chen, P., Cao, L., Li, Y., Zeng, Z., Cui, Y., Wu, Q., Li, J., Wang, J.-H., Dong, M.-Q., et al. (2020) · eLife · doi:10.7554/elife.59994 · Cited by 215
Cullin–RING ubiquitin E3 ligase regulation by the COP9 signalosome
Cavadini, S., Fischer, E. S., Bunker, R. D., Potenza, A., Lingaraju, G. M., Goldie, K. N., Mohamed, W. I., Faty, M., Petzold, G., Beckwith, R. E. J., et al. (2016) · Nature · doi:10.1038/nature17416 · Cited by 213
Self-citationChemically Induced Degradation of the Oncogenic Transcription Factor BCL6
Kerres, N., Steurer, S., Schlager, S., Bader, G., Berger, H., Caligiuri, M., Dank, C., Engen, J. R., Ettmayer, P., Fischerauer, B., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.081 · Cited by 207
Structural regulation of cullin-RING ubiquitin ligase complexes
Duda, D. M., Scott, D. C., Calabrese, M. F., Zimmerman, E. S., Zheng, N., & Schulman, B. A. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.01.003 · Cited by 205
Bjorklund, C. C., Kang, J., Amatangelo, M., Polonskaia, A., Katz, M., Chiu, H., Couto, S., Wang, M., Ren, Y., Ortiz, M., et al. (2020) · Leukemia · doi:10.1038/s41375-019-0620-8 · Cited by 205
Hagner, P. R., Man, H.-W., Fontanillo, C., Wang, M., Couto, S., Breider, M., Bjorklund, C., Havens, C. G., Lu, G., Rychak, E., et al. (2015) · Blood · doi:10.1182/blood-2015-02-628669 · Cited by 203
Unifying principles of bifunctional, proximity-inducing small molecules
Gerry, C. J., & Schreiber, S. L. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0469-1 · Cited by 199
Three-dimensional reconstruction of the 14-filament fibers of hemoglobin S
Dykes, G. W., Crepeau, R. H., & Edelstein, S. J. (1979) · Journal of Molecular Biology · doi:10.1016/0022-2836(79)90434-0 · Cited by 186
Du, X., Volkov, O. A., Czerwinski, R. M., Tan, H., Huerta, C., Morton, E. R., Rizzi, J. P., Wehn, P. M., Xu, R., Nijhawan, D., et al. (2019) · Structure · doi:10.1016/j.str.2019.10.005 · Cited by 181
Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader
Potjewyd, F., Turner, A. W., Beri, J., Rectenwald, J. M., Norris-Drouin, J. L., Cholensky, S. H., Margolis, D. M., Pearce, K. H., Herring, L. E., & James, L. I. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.11.006 · Cited by 181
Structural basis for the action of the drug trametinib at KSR-bound MEK
Khan, Z. M., Real, A. M., Marsiglia, W. M., Chow, A., Duffy, M. E., Yerabolu, J. R., Scopton, A. P., & Dar, A. C. (2020) · Nature · doi:10.1038/s41586-020-2760-4 · Cited by 178
pSILAC mass spectrometry reveals ZFP91 as IMiD-dependent substrate of the CRL4CRBN ubiquitin ligase
An, J., Ponthier, C. M., Sack, R., Seebacher, J., Stadler, M. B., Donovan, K. A., & Fischer, E. S. (2017) · Nature Communications · doi:10.1038/ncomms15398 · Cited by 176
Structural Basis for a Reciprocal Regulation between SCF and CSN
Enchev, R. I., Scott, D. C., da Fonseca, P. C. A., Schreiber, A., Monda, J. K., Schulman, B. A., Peter, M., & Morris, E. P. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.08.019 · Cited by 158
p63 is a cereblon substrate involved in thalidomide teratogenicity
Asatsuma-Okumura, T., Ando, H., De Simone, M., Yamamoto, J., Sato, T., Shimizu, N., Asakawa, K., Yamaguchi, Y., Ito, T., Guerrini, L., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0366-7 · Cited by 134
A hydrophobic ratchet entrenches molecular complexes
Hochberg, G. K. A., Liu, Y., Marklund, E. G., Metzger, B. P. H., Laganowsky, A., & Thornton, J. W. (2020) · Nature · doi:10.1038/s41586-020-3021-2 · Cited by 134
CDK12: an emerging therapeutic target for cancer
Lui, G. Y. L., Grandori, C., & Kemp, C. J. (2018) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2018-205356 · Cited by 132
Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15
Ting, T. C., Goralski, M., Klein, K., Wang, B., Kim, J., Xie, Y., & Nijhawan, D. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.079 · Cited by 123
Yamano, H., Tsurumi, C., Gannon, J., & Hunt, T. (1998) · The EMBO Journal · doi:10.1093/emboj/17.19.5670 · Cited by 107
Ahn, J., Vu, T., Novince, Z., Guerrero‐Santoro, J., Rapić-Otrin, V., & Gronenborn, A. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.133181 · Cited by 106
Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex
Matyskiela, M. E., Clayton, T., Zheng, X., Mayne, C., Tran, E., Carpenter, A., Pagarigan, B., McDonald, J., Rolfe, M., Hamann, L. G., et al. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0405-9 · Cited by 103
In vivo target protein degradation induced by PROTACs based on E3 ligase DCAF15
Li, L., Mi, D., Pei, H., Duan, Q., Wang, X., Zhou, W., Jin, J., Li, D., Liu, M., & Chen, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00245-0 · Cited by 102
Cullin E3 Ligases and Their Rewiring by Viral Factors
Mahon, C., Krogan, N., Craik, C., & Pick, E. (2014) · Biomolecules · doi:10.3390/biom4040897 · Cited by 101
E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin
Huang, H., Ceccarelli, D. F. J., Orlicky, S. M., St‐Cyr, D. J., Ziemba, A. J., Garg, P., Plamondon, S., Auer, M., Sidhu, S. S., Marinier, A., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1412 · Cited by 94
Integrative Modelling of Biomolecular Complexes
Koukos, P. I., & Bonvin, A. M. J. J. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.11.009 · Cited by 94
Structural bases of IMiD selectivity that emerges by 5-hydroxythalidomide
Furihata, H., Yamanaka, S., Honda, T., Miyauchi, Y., Asano, A., Shibata, N., Tanokura, M., Sawasaki, T., & Miyakawa, T. (2020) · Nature Communications · doi:10.1038/s41467-020-18488-4 · Cited by 89
Yamanaka, S., Murai, H., Saito, D., Abe, G., Tokunaga, E., Iwasaki, T., Takahashi, H., Takeda, H., Suzuki, T., Shibata, N., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2020105375 · Cited by 89
Selective Degradation of GSPT1 by Cereblon Modulators Identified via a Focused Combinatorial Library
Powell, C. E., Du, G., Che, J., He, Z., Donovan, K. A., Yue, H., Wang, E. S., Nowak, R. P., Zhang, T., Fischer, E. S., et al. (2020) · ACS Chemical Biology · doi:10.1021/acschembio.0c00520 · Cited by 87
Schafer, P. H., Ye, Y., Wu, L., Kosek, J., Ringheim, G., Yang, Z., Liu, L., Thomas, M., Palmisano, M., & Chopra, R. (2018) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2017-212916 · Cited by 78
Humanized cereblon mice revealed two distinct therapeutic pathways of immunomodulatory drugs
Gemechu, Y., Millrine, D., Hashimoto, S., Prakash, J., Sanchenkova, K., Metwally, H., Parajuli, G., Kang, S., & Kishimoto, T. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814446115 · Cited by 78
Schreiber, S. L. (2018) · Israel Journal of Chemistry · doi:10.1002/ijch.201800113 · Cited by 78
Bellenie, B. R., Cheung, K.-M. J., Varela, A., Pierrat, O. A., Collie, G. W., Box, G. M., Bright, M. D., Gowan, S., Hayes, A., Rodrigues, M. J., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b02076 · Cited by 74
Sijbesma, E., Visser, E., Plitzko, K., Thiel, P., Milroy, L.-G., Kaiser, M., Brunsveld, L., & Ottmann, C. (2020) · Nature Communications · doi:10.1038/s41467-020-17741-0 · Cited by 72
Small-Molecule Kinase Downregulators
Jones, L. H. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.10.011 · Cited by 69
Monomeric Targeted Protein Degraders
Hanan, E. J., Liang, J., Wang, X., Blake, R. A., Blaquiere, N., & Staben, S. T. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00093 · Cited by 69
Detecting UV‐lesions in the genome: The modular CRL4 ubiquitin ligase does it best!
Scrima, A., Fischer, E. S., Lingaraju, G. M., Böhm, K., Cavadini, S., & Thomä, N. H. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.04.064 · Cited by 66
Self-citationMolecular glue concept solidifies
Baek, K., & Schulman, B. A. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0414-3 · Cited by 61
Stabilization of protein–protein interactions by small molecules
Giordanetto, F., Schäfer, A., & Ottmann, C. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.08.005 · Cited by 55
Structural Aspects of Plant Hormone Signal Perception and Regulation by Ubiquitin Ligases
Tal, L., Gil, M. X. A., Guercio, A. M., & Shabek, N. (2020) · PLANT PHYSIOLOGY · doi:10.1104/pp.19.01282 · Cited by 53
Scherer, P. C., Ding, Y., Liu, Z., Xu, J., Mao, H., Barrow, J. C., Wei, N., Zheng, N., Snyder, S. H., & Rao, F. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525580113 · Cited by 48
Matyskiela, M. E., Zhu, J., Baughman, J. M., Clayton, T., Slade, M., Wong, H. K., Danga, K., Zheng, X., Labow, M., LeBrun, L. A., et al. (2020) · ACS Chemical Biology · doi:10.1021/acschembio.0c00674 · Cited by 45
Li, L., Xue, W., Shen, Z., Liu, J., Hu, M., Cheng, Z., Wang, Y., Chen, Y., Chang, H., Liu, Y., et al. (2020) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2020.06.013 · Cited by 41
Abstract 4452: GNE-0011, a novel monovalent BRD4 degrader
Blake, R. A. (2019) · Cancer Research · doi:10.1158/1538-7445.am2019-4452 · Cited by 29
Protein–Protein Interaction Methods and Protein Phase Separation
Savojardo, C., Martelli, P. L., & Casadio, R. (2020) · Annual Review of Biomedical Data Science · doi:10.1146/annurev-biodatasci-011720-104428 · Cited by 26
Lopez-Girona, A., Havens, C. G., Lu, G., Rychak, E., Mendy, D., Gaffney, B., Surka, C., Lu, C.-C., Matyskiela, M., Khambatta, G., et al. (2019) · Blood · doi:10.1182/blood-2019-124338 · Cited by 25
Yu, H. H., Reitsma, J. M., Sweredoski, M. J., Moradian, A., Hess, S. Y., & Deshaies, R. J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/595389 · Cited by 8
Linkers for protein degradation
Chamberlain, P. P. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0057-9 · Cited by 6
Abstract 4452: GNE-0011, a novel monovalent BRD4 degrader
Blake, R. A. (2019) · Cancer Chemistry · doi:10.1158/1538-7445.sabcs18-4452 · Cited by 6
Zemke, N. R., Barshop, W. D., Sha, J., Hsu, E., Wohlschlegel, J. A., & Berk, A. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.16.423151 · Cited by 1
Research works printed but not linked: 1
- Yamanaka, 2020, PLZF is a new substrate of CRBN with thalidomide and 5-hydroxythalidomide, BioRxiv
Cited by
Sorted by citations
PROTACs: past, present and future
Li, K., & Crews, C. M. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00193d · Cited by 869
Targeted protein degradation: from mechanisms to clinic
Tsai, J. M., Nowak, R. P., Ebert, B. L., & Fischer, E. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00729-9 · Cited by 438
Epigenetics-targeted drugs: current paradigms and future challenges
Dai, W., Qiao, X., Fang, Y., Guo, R., Bai, P., Liu, S., Li, T., Jiang, Y., Wei, S., Na, Z., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02039-0 · Cited by 405
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
Molecular Glues: The Adhesive Connecting Targeted Protein Degradation to the Clinic
Sasso, J. M., Tenchov, R., Wang, D.-S., Johnson, L. S., Wang, X., & Zhou, Q. A. (2022) · Biochemistry · doi:10.1021/acs.biochem.2c00245 · Cited by 264
Metadata
- Authors
- Kozicka, Z., & Thomä, N. H.
- Affiliations
- University of Basel (CH)
- Friedrich Miescher Institute (CH)
- Corresponding author
- Thomä, Nicolas Holger
- Venue
- Cell Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 28
- Issue
- 7
- Pages
- 1032-1047
- ISSN
- 2451-9448 (ISSN-L)
- 2451-9456
- OpenAlex
- W3158527646
- Semantic Scholar
- ae8a5b956b209af205f68e27236708f9dc194e10
- Cited by
- 170
- References
- 111
- Citations by year
- 2026: 37 · 2025: 40 · 2024: 28 · 2023: 34 · 2022: 29 · 2021: 2
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 379 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell chemical biology (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion)
- Funders
- European Research Council (666068)
- European Commission (765445)
- Horizon 2020
- Novartis Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (186230, KFS-4980-02-2020)
- Oncosuisse
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- molecular glues, E3 ubiquitin ligase, cullin-RING ubiquitin ligases, protein degradation, protein surface modification, protein-protein interaction, protein assembly, drug design, protein-protein interaction network
- MeSH terms
- Enzyme Inhibitors, Humans, Ubiquitin-Protein Ligases, Small Molecule Libraries, Ubiquitination
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