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Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4
Open accessAbstract
BRD4, a bromodomain and extraterminal domain (BET) family member, is an attractive target in multiple pathological settings, particularly cancer. While BRD4 inhibitors have shown some promise in MYC-driven malignancies such as Burkitt's lymphoma (BL), we show that BRD4 inhibitors lead to robust BRD4 protein accumulation, which may account for their limited suppression of MYC expression, modest antiproliferative activity, and lack of apoptotic induction. To address these limitations we designed ARV-825, a hetero-bifunctional PROTAC (Proteolysis Targeting Chimera) that recruits BRD4 to the E3 ubiquitin ligase cereblon, leading to fast, efficient, and prolonged degradation of BRD4 in all BL cell lines tested. Consequently, ARV-825 more effectively suppresses c-MYC levels and downstream signaling than small-molecule BRD4 inhibitors, resulting in more effective cell proliferation inhibition and apoptosis induction in BL. Our findings provide strong evidence that cereblon-based PROTACs provide a better and more efficient strategy in targeting BRD4 than traditional small-molecule inhibitors.
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“These results are in agreement with the unique mechanism of action of PROTACs, that usually have a longer-lasting effect and require less systemic drug exposure to be effective than their corresponding “payloads”.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [39]
In the citing paper
“This is because PROTACs act catalytically to induce protein degradation in a sub-stoichiometric manner and their effect is not limited by equilibrium occupancy32,39.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [39]
In the citing paper
“We used a less intensive dosing schedule (i.e., 41 μmol/kg, once every 3 days or q3d) for this experiment because PZ functioning as a PROTAC has a longer-acting activity than its corresponding inhibitor39 (Fig. 3b).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [39]
In the citing paper
“ARV825 is a hetero-bifunctional PROTAC (Proteolysis Targeting Chimera) that recruits BET family proteins to the E3 ubiquitin ligase CEREBLON, leading to the fast, efficient, and prolonged degradation of BET family proteins24.”
From A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells (2020) · cites this paper as [24]
In the citing paper
“In addition, long-term dosing or high concentrations associated with BETi treatment also leads to obvious BRD4 protein accumulation and inefficient c-MYC suppression [85].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [85]
In the citing paper
“For example, PROTACs against BRD4, BTK, BCR-ABL and CDK-6 etc. have shown efficacy in leukemia [22, 44, 58, 60], whereas AR, ER, FAK, P38 PROTACs have been developed against different solid tumors [13, 49, 51, 104] (Table 1).”
From PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics (2020) · cites this paper as [22]
In the citing paper
“PROTACs consisting of pomalidomide and OTX015 [84] or JQ1 [85] resulted in robust BRD4 degradation when used at low nanomolar concentrations [84, 85].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [84]
In the citing paper
“Concomitantly, c-Myc levels were strongly depleted, and this depletion lasted longer after washout of the PROTAC than after inhibitor treatment [84].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [84]
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Cites
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers
Lovén, J., Hoke, H. A., Lin, C. Y., Lau, A., Orlando, D. A., Vakoc, C. R., Bradner, J. E., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.036 · Cited by 2,961
BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.017 · Cited by 2,888
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
Self-citationIdentification 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
RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
Zuber, J., Shi, J., Wang, E., Rappaport, A. R., Herrmann, H., Sison, E. A., Magoon, D., Qi, J., Blatt, K., Wunderlich, M., et al. (2011) · Nature · doi:10.1038/nature10334 · Cited by 1,870
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
Targeting MYC dependence in cancer by inhibiting BET bromodomains
Mertz, J. A., Conery, A. R., Bryant, B. M., Sandy, P., Balasubramanian, S., Mele, D. A., Bergeron, L., & Sims, R. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108190108 · Cited by 1,145
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
Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer
Asangani, I. A., Dommeti, V. L., Wang, X., Malik, R., Cieslik, M. P., Yang, R., Escara-Wilke, J. F., Wilder-Romans, K., Dhanireddy, S., Engelke, C. G., et al. (2014) · Nature · doi:10.1038/nature13229 · Cited by 941
Research works printed but not linked: 2
- Ge, 2007, Process for the preparation of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione compounds, US Pat. Appl.
- Sueoka, 1998, Preparation and formulation of thienotriazolodiazepine derivatives for the treatment of inflammatory intestinal diseases, venous insufficiency, and venous ulcer, PCT Int. Appl.
Cited by
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Zheng, N., & Shabek, N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014922 · Cited by 1,499
Induced 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
Self-citationStructural 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
The dTAG system for immediate and target-specific protein degradation
Nabet, B., Roberts, J. M., Buckley, D. L., Paulk, J., Dastjerdi, S., Yang, A., Leggett, A. L., Erb, M. A., Lawlor, M. A., Souza, A., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0021-8 · Cited by 1,118
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
Self-citationProteome-wide covalent ligand discovery in native biological systems
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., et al. (2016) · Nature · doi:10.1038/nature18002 · Cited by 940
Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead
Bondeson, D. P., Smith, B. E., Burslem, G. M., Buhimschi, A. D., Hines, J., Jaime-Figueroa, S., Wang, J., Hamman, B. D., Ishchenko, A., & Crews, C. M. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.09.010 · Cited by 923
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Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867
PROTACs: past, present and future
Li, K., & Crews, C. M. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00193d · Cited by 869
Self-citationPROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer
Raina, K., Lu, J., Qian, Y., Altieri, M., Gordon, D., Rossi, A. M. K., Wang, J., Chen, X., Dong, H., Siu, K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521738113 · Cited by 852
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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
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Khan, S., Zhang, X., Lv, D., Zhang, Q., He, Y., Zhang, P., Liu, X., Thummuri, D., Yuan, Y., Wiegand, J. S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0668-z · Cited by 688
The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study
Burslem, G. M., Smith, B. E., Lai, A. C., Jaime-Figueroa, S., McQuaid, D. C., Bondeson, D. P., Toure, M., Dong, H., Qian, Y., Wang, J., et al. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.09.009 · Cited by 686
Self-citationSmall‐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
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Bai, L., Zhou, H., Xu, R., Zhao, Y., Chinnaswamy, K., McEachern, D., Chen, J., Yang, C.-Y., Liu, Z., Wang, M., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.002 · Cited by 652
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Chirnomas, D., Hornberger, K. R., & Crews, C. M. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00736-3 · Cited by 658
Self-citationStructural 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
Modular PROTAC design for the degradation of oncogenic BCR-ABL
Lai, A. C., Toure, M., Hellerschmied, D., Salami, J., Jaime‐Figueroa, S., Ko, E., Hines, J., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507634 · Cited by 618
Self-citationPlasticity 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
Targeted protein degradation by PROTACs
Neklesa, T. K., Winkler, J. D., & Crews, C. M. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.027 · Cited by 599
Self-citationCotton, A. D., Nguyen, D. P., Gramespacher, J. A., Seiple, I. B., & Wells, J. A. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.0c10008 · Cited by 551
Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation
Olson, C. M., Jiang, B., Erb, M. A., Liang, Y., Doctor, Z. M., Zhang, Z., Zhang, T., Kwiatkowski, N., Boukhali, M., Green, J. L., et al. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2538 · Cited by 552
Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase
Smith, B. E., Wang, S. L., Jaime-Figueroa, S., Harbin, A., Wang, J., Hamman, B. D., & Crews, C. M. (2019) · Nature Communications · doi:10.1038/s41467-018-08027-7 · Cited by 517
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
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Stanton, B. Z., Chory, E. J., & Crabtree, G. R. (2018) · Science · doi:10.1126/science.aao5902 · Cited by 475
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Stathis, A., & Bertoni, F. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0605 · Cited by 463
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
Winter, G. E., Mayer, A., Buckley, D. L., Erb, M. A., Roderick, J. E., Vittori, S., Reyes, J. M., di Iulio, J., Souza, A., Ott, C. J., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.06.004 · Cited by 465
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Self-citationDrugging the undruggables: exploring the ubiquitin system for drug development
Huang, X., & Dixit, V. M. (2016) · Cell Research · doi:10.1038/cr.2016.31 · Cited by 427
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Huang, H.-T., Dobrovolsky, D., Paulk, J., Yang, G., Weisberg, E. L., Doctor, Z. M., Buckley, D. L., Cho, J.-H., Ko, E., Jang, J., et al. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.10.005 · Cited by 437
Harnessing 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
Protein Degradation by In-Cell Self-Assembly of Proteolysis Targeting Chimeras
Lebraud, H., Wright, D. J., Johnson, C. N., & Heightman, T. D. (2016) · ACS Central Science · doi:10.1021/acscentsci.6b00280 · Cited by 413
Delineating the role of cooperativity in the design of potent PROTACs for BTK
Zorba, A., Nguyen, C., Xu, Y., Starr, J., Borzilleri, K., Smith, J., Zhu, H., Farley, K. A., Ding, W., Schiemer, J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803662115 · Cited by 419
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
Edmondson, S. D., Yang, B., & Fallan, C. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.04.030 · Cited by 422
Current strategies for the design of PROTAC linkers: a critical review
Troup, R. I., Fallan, C., & Baud, M. G. J. (2020) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2020.00018 · Cited by 424
Buhimschi, A. D., Armstrong, H. A., Toure, M., Jaime-Figueroa, S., Chen, T. L., Lehman, A. M., Woyach, J. A., Johnson, A. J., Byrd, J. C., & Crews, C. M. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00391 · Cited by 394
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Xue, G., Wang, K., Zhou, D., Zhong, H., & Pan, Z. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b06422 · Cited by 377
An, S., & Fu, L. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.09.005 · Cited by 363
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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
Self-citationZhang, L., Riley-Gillis, B., Vijay, P., & Shen, Y. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-1129 · Cited by 365
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Hines, J., Lartigue, S., Dong, H., Qian, Y., & Crews, C. M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2918 · Cited by 348
Self-citationZoppi, V., Hughes, S. J., Maniaci, C., Testa, A., Gmaschitz, T., Wieshofer, C., Koegl, M., Riching, K. M., Daniels, D. L., Spallarossa, A., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01413 · Cited by 336
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Li, Y., Yang, J., Aguilar, A., McEachern, D., Przybranowski, S., Liu, L., Yang, C.-Y., Wang, M., Han, X., & Wang, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00909 · Cited by 312
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Sun, Y., Zhao, X., Ding, N., Gao, H., Wu, Y., Yang, Y., Zhao, M., Hwang, J., Song, Y., Liu, W., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0055-1 · Cited by 295
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Self-citationHe, Y., Zhang, X., Chang, J., Kim, H.-N., Zhang, P., Wang, Y., Khan, S., Liu, X., Zhang, X., Lv, D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15838-0 · Cited by 280
Crew, A. P., Raina, K., Dong, H., Qian, Y., Wang, J., Vigil, D., Serebrenik, Y. V., Hamman, B. D., Morgan, A., Ferraro, C., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00635 · Cited by 257
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Maniaci, C., Hughes, S. J., Testa, A., Chen, W., Lamont, D. J., Rocha, S., Alessi, D. R., Romeo, R., & Ciulli, A. (2017) · Nature Communications · doi:10.1038/s41467-017-00954-1 · Cited by 245
Hughes, S. J., & Ciulli, A. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170041 · Cited by 240
Ohoka, N., Okuhira, K., Ito, M., Nagai, K., Shibata, N., Hattori, T., Ujikawa, O., Shimokawa, K., Sano, O., Koyama, R., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.768853 · Cited by 240
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
Zhou, H., Bai, L., Xu, R., Zhao, Y., Chen, J., McEachern, D., Chinnaswamy, K., Wen, B., Dai, L., Kumar, P., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01530 · Cited by 233
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Gu, S., Cui, D., Chen, X., Xiong, X., & Zhao, Y. (2018) · BioEssays · doi:10.1002/bies.201700247 · Cited by 231
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Zaidman, D., Prilusky, J., & London, N. (2020) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00589 · Cited by 224
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Gechijian, L. N., Buckley, D. L., Lawlor, M. A., Reyes, J. M., Paulk, J., Ott, C. J., Winter, G. E., Erb, M. A., Scott, T. G., Xu, M., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0010-y · Cited by 222
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Hu, Z., & Crews, C. M. (2022) · ChemBioChem · doi:10.1002/cbic.202100270 · Cited by 231
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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
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Wakita, M., Takahashi, A., Sano, O., Loo, T. M., Imai, Y., Narukawa, M., Iwata, H., Matsudaira, T., Kawamoto, S., Ohtani, N., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15719-6 · Cited by 206
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Ding, Y., Fei, Y., & Lu, B. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.04.005 · Cited by 204
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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
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Ichikawa, S., Flaxman, H. A., Xu, W., Vallavoju, N., Lloyd, H. C., Wang, B., Shen, D., Pratt, M. R., & Woo, C. M. (2022) · Nature · doi:10.1038/s41586-022-05333-5 · Cited by 195
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Bai, L., Zhou, B., Yang, C.-Y., Ji, J., McEachern, D., Przybranowski, S., Jiang, H., Hu, J., Xu, F., Zhao, Y., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2622 · Cited by 199
Chasing molecular glue degraders: screening approaches
Domostegui, A., Nieto-Barrado, L., Perez-Lopez, C., & Mayor-Ruiz, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00197g · Cited by 200
Yang, J., Li, Y., Aguilar, A., Liu, Z., Yang, C.-Y., & Wang, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00846 · Cited by 190
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Liu, J., Ma, J., Liu, Y., Xia, J., Li, Y., Wang, Z. P., & Wei, W. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.02.006 · Cited by 186
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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
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Wu, H., Yang, K., Zhang, Z., Leisten, E. D., Li, Z., Xie, H., Liu, J., Smith, K. A., Novakova, Z., Barinka, C., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00516 · Cited by 180
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Yang, K., Song, Y., Xie, H., Wu, H., Wu, Y.-T., Leisten, E. D., & Tang, W. (2018) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2018.05.057 · Cited by 190
Han, X., Zhao, L., Xiang, W., Qin, C., Miao, B., McEachern, D., Wang, Y., Metwally, H., Wang, L., Matvekas, A., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00882 · Cited by 170
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Vannam, R., Sayilgan, J., Ojeda, S., Karakyriakou, B., Hu, E., Kreuzer, J., Morris, R., Herrera Lopez, X. I., Rai, S., Haas, W., et al. (2021) · Cell Chemical Biology · doi:10.1016/j.chembiol.2020.12.004 · Cited by 177
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Dobrovolsky, D., Wang, E. S., Morrow, S., Leahy, C., Faust, T., Nowak, R. P., Donovan, K. A., Yang, G., Li, Z., Fischer, E. S., et al. (2019) · Blood · doi:10.1182/blood-2018-07-862953 · Cited by 169
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Bai, N., Miller, S. A., Andrianov, G. V., Yates, M., Kirubakaran, P., & Karanicolas, J. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c01451 · Cited by 157
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Li, F., Hu, Q., Zhang, X., Sun, R., Liu, Z., Wu, S., Tian, S., Ma, X., Dai, Z., Yang, X., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34807-3 · Cited by 159
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Alabi, S., Jaime-Figueroa, S., Yao, Z., Gao, Y., Hines, J., Samarasinghe, K. T. G., Vogt, L., Rosen, N., & Crews, C. M. (2021) · Nature Communications · doi:10.1038/s41467-021-21159-7 · Cited by 152
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He, Y., Koch, R., Budamagunta, V., Zhang, P., Zhang, X., Khan, S., Thummuri, D., Ortiz, Y. T., Zhang, X., Lv, D., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00928-9 · Cited by 139
McCoull, W., Cheung, T., Anderson, E., Barton, P., Burgess, J., Byth, K., Cao, Q., Castaldi, M. P., Chen, H., Chiarparin, E., et al. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.8b00698 · Cited by 139
Popow, J., Arnhof, H., Bader, G., Berger, H., Ciulli, A., Covini, D., Dank, C., Gmaschitz, T., Greb, P., Karolyi-Özguer, J., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01826 · Cited by 138
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Liang, K., Smith, E. R., Aoi, Y., Stoltz, K. L., Katagi, H., Woodfin, A. R., Rendleman, E. J., Marshall, S. A., Murray, D. C., Wang, L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.027 · Cited by 124
Sievers, Q. L., Gasser, J. A., Cowley, G. S., Fischer, E. S., & Ebert, B. L. (2018) · Blood · doi:10.1182/blood-2018-01-821769 · Cited by 124
Metadata
- Authors
- Lu, J., Qian, Y., Altieri, M., Dong, H., Wang, J., Raina, K., Hines, J., Winkler, J. D., Crew, A. P., Coleman, K., & Crews, C. M.
- Affiliations
- Arvinas (United States) (US)
- Yale University (US)
- Corresponding author
- Crews, Craig M.
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 22
- Issue
- 6
- Pages
- 755-763
- ISSN
- 1074-5521 (ISSN-L)
- PMC
- PMC4475452
- OpenAlex
- W1488181101
- Cited by
- 1,140
- References
- 37
- Citations by year
- 2026: 75 · 2025: 101 · 2024: 135 · 2023: 104 · 2022: 134 · 2021: 118 · 2020: 151 · 2019: 119 · 2018: 77 · 2017: 71 · 2016: 40 · 2015: 10
- FWCI
- 29.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Chemistry & Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI084140, R01AI084140)
- 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
- BRD4, cereblon, PROTACs, E3 ubiquitin ligase, Burkitt lymphoma, c-Myc, BET proteins, BRD4 inhibitors, protein degradation, apoptosis, cell proliferation inhibition
- MeSH terms
- Acetanilides, Bromodomain Containing Proteins, Azepines, Heterocyclic Compounds, 3-Ring, Humans, Nuclear Proteins, Peptide Hydrolases, Thalidomide, Transcription Factors, Triazoles, Signal Transduction, Proto-Oncogene Proteins c-myc, Apoptosis, Cell Cycle Proteins, Ubiquitin-Protein Ligases, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Cell Proliferation
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