Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery
Abstract
Targeted protein degradation is a promising area in the discovery and development of innovative therapeutics. Molecular glues mediate proximity-induced protein degradation and have intrinsic advantages over heterobifunctional proteolysis-targeting chimeras, including unprecedented mechanisms, distinct biological activities, and favorable physicochemical properties. Classical molecular glue degraders have been identified serendipitously, but rational discovery and design strategies are emerging rapidly. In this review, we aim to highlight the recent advances in molecular glues for targeted protein degradation and discuss the challenges in developing molecular glues into therapeutic agents. In particular, discovery strategies, action mechanisms, and representative case studies will be addressed.
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Examples of strategies for the systematic development or identification of novel MG degraders are still limited.
“Examples of strategies for the systematic development or identification of novel MG degraders are still limited.152”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [152]
Cites
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452 · see citing works
Lead- and drug-like compounds: the rule-of-five revolution
Lipinski, C. A. (2004) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2004.11.007 · Cited by 6,339 · see citing works
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 · see citing works
Next-generation characterization of the Cancer Cell Line Encyclopedia
Ghandi, M., Huang, F. W., Jané-Valbuena, J., Kryukov, G. V., Lo, C. C., McDonald, E. R., Barretina, J., Gelfand, E. T., Bielski, C. M., Li, H., et al. (2019) · Nature · doi:10.1038/s41586-019-1186-3 · Cited by 3,394 · see citing works
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 · 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
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationInduced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486 · see citing works
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 · see citing works
Targeted protein degradation: expanding the toolbox
Schapira, M., Calabrese, M. F., Bullock, A. N., & Crews, C. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0047-y · Cited by 960 · see citing works
Structure of the FKBP12-Rapamycin Complex Interacting with Binding Domain of Human FRAP
Choi, J., Chen, J., Schreiber, S. L., & Clardy, J. (1996) · Science · doi:10.1126/science.273.5272.239 · Cited by 933 · see citing works
Discovering the anticancer potential of non-oncology drugs by systematic viability profiling
Corsello, S. M., Nagari, R. T., Spangler, R. D., Rossen, J., Kocak, M., Bryan, J. G., Humeidi, R., Peck, D., Wu, X., Tang, A. A., et al. (2020) · Nature Cancer · doi:10.1038/s43018-019-0018-6 · Cited by 878 · see citing works
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 · see citing works
X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex
Griffith, J. P., Kim, J. L., Kim, E. E., Sintchak, M. D., Thomson, J. A., Fitzgibbon, M. J., Fleming, M. A., Caron, P. R., Hsiao, K., & Navia, M. A. (1995) · Cell · doi:10.1016/0092-8674(95)90439-5 · Cited by 834 · see citing works
PROteolysis TArgeting Chimeras (PROTACs) — Past, present and future
Pettersson, M., & Crews, C. M. (2019) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2019.01.002 · Cited by 818 · see citing works
Lopez-Girona, A., Mendy, D., Ito, T., Miller, K., Gandhi, A. K., Kang, J., Karasawa, S., Carmel, G., Jackson, P., Abbasian, M., et al. (2012) · Leukemia · doi:10.1038/leu.2012.119 · Cited by 814 · see citing works
The evolution of thalidomide and its IMiD derivatives as anticancer agents
Bartlett, J. B., Dredge, K. S., & Dalgleish, A. G. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1323 · Cited by 811 · see citing works
Crystal structures of human calcineurin and the human FKBP12–FK506–calcineurin complex
Kissinger, C. R., Parge, H. E., Knighton, D. R., Lewis, C. T., Pelletier, L. A., Tempczyk, A., Kalish, V. J., Tucker, K. D., Showalter, R. E., Moomaw, E. W., et al. (1995) · Nature · doi:10.1038/378641a0 · Cited by 762 · see citing works
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 · see citing works
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 · see citing works
Small‐Molecule PROTACS: New Approaches to Protein Degradation
Toure, M., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507978 · Cited by 674 · see citing works
Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma
Rajkumar, S. V., Hayman, S. R., Lacy, M. Q., Dispenzieri, A., Geyer, S. M., Kabat, B., Zeldenrust, S. R., Kumar, S., Greipp, P. R., Fonseca, R., et al. (2005) · Blood · doi:10.1182/blood-2005-07-2817 · Cited by 648 · see citing works
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 · see citing works
Gandhi, 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 · see citing works
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 · see citing works
Schreiber, S. L. (2021) · Cell · doi:10.1016/j.cell.2020.12.020 · Cited by 598 · see citing works
Targeted protein degradation: elements of PROTAC design
Paiva, S.-L., & Crews, C. M. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.02.022 · Cited by 586 · see citing works
Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds
Li, Z., Wang, C., Wang, Z., Zhu, C., Li, J., Sha, T., Ma, L., Gao, C., Yang, Y., Sun, Y., et al. (2019) · Nature · doi:10.1038/s41586-019-1722-1 · Cited by 551 · see citing works
Self-citationDefining 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 · see citing works
Chamberlain, 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 · see citing works
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 · see citing works
Protac-Induced Protein Degradation in Drug Discovery: Breaking the Rules or Just Making New Ones?
Churcher, I. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01272 · Cited by 491 · see citing works
Development of targeted protein degradation therapeutics
Chamberlain, P. P., & Hamann, L. G. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0362-y · Cited by 489 · see citing works
Chemically induced proximity in biology and medicine
Stanton, B. Z., Chory, E. J., & Crabtree, G. R. (2018) · Science · doi:10.1126/science.aao5902 · Cited by 475 · see citing works
The 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 · see citing works
Edmondson, S. D., Yang, B., & Fallan, C. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.04.030 · Cited by 422 · see citing works
Selective 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 · see citing works
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 · see citing works
Yu, C., Mannan, A. M., Yvone, G. M., Ross, K. N., Zhang, Y.-L., Marton, M. A., Taylor, B. R., Crenshaw, A., Gould, J. Z., Tamayo, P., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3460 · Cited by 362 · see citing works
SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate
Matyskiela, M. E., Couto, S., Zheng, X., Lu, G., Hui, J., Stamp, K., Drew, C., Ren, Y., Wang, M., Carpenter, A., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0129-x · Cited by 338 · see citing works
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 · see citing works
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 · see citing works
The PROTAC technology in drug development
Zou, Y., Ma, D., & Wang, Y. (2019) · Cell Biochemistry and Function · doi:10.1002/cbf.3369 · Cited by 307 · see citing works
Solution Structure of FKBP, a Rotamase Enzyme and Receptor for FK506 and Rapamycin
Michnick, S. W., Rosen, M. K., Wandless, T. J., Karplus, M., & Schreiber, S. L. (1991) · Science · doi:10.1126/science.1709301 · Cited by 303 · see citing works
Zhu, Y. X., Kortuem, K. M., & Stewart, A. K. (2013) · Leukemia & Lymphoma · doi:10.3109/10428194.2012.728597 · Cited by 293 · see citing works
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 · see citing works
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 · see citing works
Unraveling the Role of Linker Design in Proteolysis Targeting Chimeras
Bemis, T. A., Clair, J. J. L., & Burkart, M. D. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00482 · Cited by 244 · see citing works
Hansen, J. D., Correa, M., Nagy, M. A., Alexander, M., Plantevin, V., Grant, V., Whitefield, B., Huang, D., Kercher, T., Harris, R., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01928 · Cited by 240 · see citing works
Surka, 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 · see citing works
Proteolysis-Targeting Chimeras: Induced Protein Degradation as a Therapeutic Strategy
Ottis, P., & Crews, C. M. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.6b01068 · Cited by 227 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Chemically 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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Hansen, J. D., Correa, M., Alexander, M., Nagy, M., Huang, D., Sapienza, J., Lu, G., LeBrun, L. A., Cathers, B. E., Zhang, W., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01489 · Cited by 159 · see citing works
E7070, a novel sulphonamide agent with potent antitumour activity in vitro and in vivo
Ozawa, Y., Sugi, N. H., Nagasu, T., Owa, T., Watanabe, T., Koyanagi, N., Yoshino, H., Kitoh, K., & Yoshimatsu, K. (2001) · European Journal of Cancer · doi:10.1016/s0959-8049(01)00275-1 · Cited by 132 · 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
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 · see citing works
Cereblon modulators: Low molecular weight inducers of protein degradation
Chamberlain, P. P., & Cathers, B. E. (2019) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2019.02.004 · Cited by 106 · see citing works
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 · see citing works
Thalidomide-analogue biology: immunological, molecular and epigenetic targets in cancer therapy
Shortt, J., Hsu, A. K., & Johnstone, R. W. (2013) · Oncogene · doi:10.1038/onc.2012.599 · Cited by 101 · see citing works
Bifunctional chemical probes inducing protein–protein interactions
Maniaci, C., & Ciulli, A. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.07.003 · Cited by 100 · see citing works
Lin, X., Xiang, H., & Luo, G. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112689 · Cited by 100 · see citing works
Talbot, D. C., von Pawel, J., Cattell, E., Yule, S. M., Johnston, C., Zandvliet, A. S., Huitema, A. D. R., Norbury, C. J., Ellis, P., Bosquée, L., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0249 · Cited by 82 · see citing works
Hansen, J. D., Condroski, K. R., Correa, M., Muller, G. W., Man, H., Ruchelman, A. L., Zhang, W., Vocanson, F., Crea, T., Liu, W., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01911 · Cited by 78 · see citing works
Inducing protein-protein interactions with molecular glues
Che, Y., Gilbert, A. M., Shanmugasundaram, V., & Noe, M. C. (2018) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2018.04.046 · Cited by 71 · see citing works
Haddad, R. I., Weinstein, L. J., Wieczorek, T. J., Bhattacharya, N., Raftopoulos, H., Oster, M. W., Zhang, X., Latham, V. M., Costello, R., Faucher, J., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0229 · Cited by 66 · see citing works
Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma
Martiniani, R., Loreto, V. D., Sano, C. D., Lombardo, A., & Liberati, A. M. (2012) · Advances in Hematology · doi:10.1155/2012/842945 · Cited by 65 · see citing works
Molecular glue concept solidifies
Baek, K., & Schulman, B. A. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0414-3 · Cited by 61 · see citing works
Raymond, É., Huinink, W. W. T. B., Taı̈eb, J., Beijnen, J. H., Faivre, S. J., Wanders, J., Ravic, M., Fumoleau, P., Armand, J., & Schellens, J. H. M. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.09.030 · Cited by 60 · see citing works
Ozawa, Y., Kusano, K., Owa, T., Yokoi, A., Asada, M., & Yoshimatsu, K. (2012) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-012-1844-8 · Cited by 59 · see citing works
A critical evaluation of the approaches to targeted protein degradation for drug discovery
Chopra, R., Sadok, A., & Collins, I. (2019) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2019.02.002 · Cited by 53 · see citing works
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- Authors
- Dong, G., Ding, Y., He, S., & Sheng, C.
- Affiliations
- Second Military Medical University (CN)
- Shanghai Medical College of Fudan University (CN)
- Shanghai University (CN)
- Corresponding author
- Sheng, Chunquan
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-07-28
- Volume
- 64
- Issue
- 15
- Pages
- 10606-10620
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W3186572052
- Semantic Scholar
- 0c0dcbeddb2625c9bf7bcdb2b5e4eb42f5103c19
- Cited by
- 369
- References
- 78
- Citations by year
- 2026: 75 · 2025: 96 · 2024: 72 · 2023: 74 · 2022: 49 · 2021: 3
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2017YFA0506000)
- National Natural Science Foundation of China (81725020, 82030105, 82030106)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- molecular glues, targeted protein degradation, PROTACs, rational drug design, treatment development
- MeSH terms
- Acetamides, Humans, Piperidones, Proteins, Molecular Structure, Isoindoles, Drug Discovery, Proteolysis
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 ›
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