Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK)
Open accessAbstract
Anaplastic lymphoma kinase (ALK) activation has been associated with many types of human cancer. Significant efforts have been devoted to the development of ALK inhibitors to antagonize the kinase activity of ALK. Four ALK inhibitors have been approved by the FDA to date for treating patients with ALK-positive non-small cell lung cancers (NSCLC). However, drug resistance has been observed in the majority of patients treated with these inhibitors. New therapeutic strategies (e.g., compounds with novel mechanisms of action) are needed to overcome the drug resistance issue. The emerging PROTAC (Proteolysis Targeting Chimera) technology has been successfully applied to selective degradation of multiple protein targets, but not ALK. Since ALK protein levels are not important for viability in mammals, ALK PROTACs could lead to novel therapeutics with minimal toxicity. Here we report the design, synthesis and biological evaluation of novel PROTACs (degraders) of ALK. MS4077 (5) and MS4078 (6) potently decreased cellular levels of oncogenic active ALK fusion proteins in a concentration- and time-dependent manner in SU-DHL-1 lymphoma and NCI-H2228 lung cancer cells. The ALK protein degradation induced by compounds 5 and 6 was cereblon and proteasome dependent. In addition, compounds 5 and 6 potently inhibited proliferation of SU-DHL-1 cells. Furthermore, compound 6 displayed good plasma exposure in a mouse pharmacokinetic study, thus is suitable for in vivo efficacy studies. We also developed MS4748 (7) and MS4740 (8), very close analogs of 5 and 6 respectively, which are incapable to degrade the ALK fusion proteins, as negative controls. Compounds 5-8 are valuable chemical tools for investigating effects of ALK pharmacological degradation. Our study paved the way for developing the next generation of ALK PROTACs.
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PROTACs were shown to be substrates for MDR1.
“Recently, PROTACs were shown to be substrates for MDR1 (10, 13), suggesting that drug efflux represents a potential limitation for degrader therapies.”
From The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells (2022) · cites this paper as [13]
A number of PROTACs have been developed to target various proteins of interest involved in the tumorigenesis and progression of hematologic malignancies, including ALK, Bcl-xL, BCR-ABL, BTK, BRD4, CDK-6, FLT-3, HDAC6, and STAT3.
“A number of PROTACs have been developed to target various POIs that are involved in the tumorigenesis and progression of hematologic malignancies, such as anaplastic lymphoma kinase (ALK) [5], Bcl-xL [4], BCR-ABL [6], Bruton’s tyrosine kinase (BTK) [7], BRD4 [8], CDK-6 [9], FMS-like tyrosine kinase-3 (FLT-3) [10], HDAC6 [11], and signal transducer and activator of transcription 3 (STAT3) [3].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [5]
ALK was degraded by two PROTACs based on a pomalidomide warhead targeting CRBN linked with either LDK378 (ceritinib) or TAE684.
“Recently, the anaplastic lymphoma kinase (ALK) was degraded by two PROTACs based on a pomalidomide warhead targeting CRBN linked with either LDK378 (ceritinib) [79, 80] or TAE684 [79] targeting ALK.”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [80]
Both PROTACs reduced downstream signalling and proliferation of ALK-driven cell lines by degrading ALK.
“Both PROTACs were able to reduce downstream signalling and proliferation of ALK-driven cell lines by degrading ALK [79, 80].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [80]
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Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Soda, M., Choi, Y. L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S.-I., Watanabe, H., Kurashina, K., Hatanaka, H., et al. (2007) · Nature · doi:10.1038/nature05945 · Cited by 5,439 · see citing works
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Kwak, E. L., Bang, Y., Camidge, D. R., Shaw, A. T., Solomon, B., Maki, R. G., Ou, S. I., Dezube, B. J., Janne, P. A., Costa, D. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1006448 · Cited by 4,442 · see citing works
First-Line Crizotinib versus Chemotherapy in <i>ALK</i> -Positive Lung Cancer
Solomon, B. J., Mok, T., Kim, D.-W., Wu, Y.-L., Nakagawa, K., Mekhail, T., Felip, E., Cappuzzo, F., Paolini, J., Usari, T., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408440 · Cited by 3,190 · see citing works
Alectinib versus Crizotinib in Untreated <i>ALK</i> -Positive Non–Small-Cell Lung Cancer
Peters, S., Camidge, D. R., Shaw, A. T., Gadgeel, S., Ahn, J. S., Kim, D.-W., Ou, S.-H. I., Pérol, M., Dziadziuszko, R., Rosell, R., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1704795 · Cited by 2,527 · see citing works
Fusion of a Kinase Gene, ALK , to a Nucleolar Protein Gene, NPM , in Non-Hodgkin's Lymphoma
Morris, S. W., Kirstein, M. N., Valentine, M. B., Dittmer, K., Shapiro, D. N., Saltman, D. L., & Look, A. T. (1994) · Science · doi:10.1126/science.8122112 · Cited by 2,404 · see citing works
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 · see citing works
A small molecule–kinase interaction map for clinical kinase inhibitors
Fabian, M. A., Biggs, W., Treiber, D. K., Atteridge, C. E., Azimioara, M. D., Benedetti, M. G., Carter, T. A., Ciceri, P., Edeen, P. T., Floyd, M. B., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1068 · Cited by 1,901 · see citing works
Ceritinib in <i>ALK</i> -Rearranged Non–Small-Cell Lung Cancer
Shaw, A. T., Kim, D.-W., Mehra, R., Tan, D. S. W., Felip, E., Chow, L. Q. M., Camidge, D. R., Vansteenkiste, J., Sharma, S., De Pas, T., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1311107 · Cited by 1,495 · see citing works
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 · see citing works
Proteasome inhibitors: valuable new tools for cell biologists.
Lee, D. H., & Goldberg, A. L. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01346-4 · Cited by 1,474 · see citing works
Identification of ALK as a major familial neuroblastoma predisposition gene
Mossé, Y. P., Laudenslager, M., Longo, L., Cole, K. A., Wood, A., Attiyeh, E. F., Laquaglia, M. J., Sennett, R., Lynch, J. E., Perri, P., et al. (2008) · Nature · doi:10.1038/nature07261 · Cited by 1,407 · see citing works
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 · see citing works
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 · see citing works
EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors
Choi, Y. L., Soda, M., Yamashita, Y., Ueno, T., Takashima, J., Nakajima, T., Yatabe, Y., Takeuchi, K., Hamada, T., Haruta, H., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1007478 · Cited by 1,186 · 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
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
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 · see citing works
Oncogenic mutations of ALK kinase in neuroblastoma
Chen, Y., Takita, J., Choi, Y. L., Kato, M., Ohira, M., Sanada, M., Wang, L., Soda, M., Kikuchi, A., Igarashi, T., et al. (2008) · Nature · doi:10.1038/nature07399 · Cited by 915 · see citing works
Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma
Janoueix‐Lerosey, I., Lequin, D., Brugières, L., Ribeiro, A., de Pontual, L., Combaret, V., Raynal, V., Puisieux, A., Schleiermacher, G., Pierron, G., et al. (2008) · Nature · doi:10.1038/nature07398 · Cited by 893 · see citing works
Activating mutations in ALK provide a therapeutic target in neuroblastoma
George, R. E., Sanda, T., Hanna, M., Fröhling, S., II, W. L., Zhang, J., Ahn, Y., Zhou, W., London, W. B., McGrady, P., et al. (2008) · Nature · doi:10.1038/nature07397 · Cited by 893 · see citing works
The ALK Inhibitor Ceritinib Overcomes Crizotinib Resistance in Non–Small Cell Lung Cancer
Friboulet, L., Li, N., Katayama, R., Lee, C. C., Gainor, J. F., Crystal, A., Michellys, P., Awad, M. M., Yanagitani, N., Kim, S., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0846 · Cited by 847 · see citing works
Iwahara, T., Fujimoto, J., Wen, D., Cupples, R. L., Bucay, N., Arakawa, T., Mori, S., Ratzkin, B. J., & Yamamoto, T. S. (1997) · Oncogene · doi:10.1038/sj.onc.1200849 · Cited by 725 · see citing works
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 · 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
Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology
Hallberg, B., & Palmer, R. H. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3580 · Cited by 643 · see citing works
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 · see citing works
Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.
Griffin, C. A., Hawkins, A. L., Dvorak, C. C., Henkle, C., Ellingham, T. J., & Perlman, E. J. (1999) · PubMed · Cited by 571 · see citing works
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 · cited 4× · see citing works
“pan kinase PROTACs [33, 34], most of kinase PROTACs reported to date target specific kinases, such as RIPK2 [35], BCR-ABL [36, 37], CDK9 [38, 39], TBK1 [40], FLT3 [33], BTK [33], EGFR [41], HER2 [41], and c-Met [41].”
BackgroundInfluentialSelf-citationTargeting ALK: Precision Medicine Takes on Drug Resistance
Lin, J. J., Riely, G. J., & Shaw, A. T. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1123 · Cited by 528 · see citing works
A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader
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 · see citing works
Marsilje, T. H., Pei, W., Chen, B., Lu, W., Uno, T., Jin, Y., Jiang, T., Kim, S., Li, N., Warmuth, M., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400402q · Cited by 422 · see citing works
Zhou, B. N., Hu, J., Xu, F., Chen, Z., Bai, L., Fernández‐Salas, E., Lin, M., Liu, L., Yang, C., Zhao, Y., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01816 · Cited by 373 · see citing works
Overall Genomic Pattern Is a Predictor of Outcome in Neuroblastoma
Janoueix‐Lerosey, I., Schleiermacher, G., Michels, E., Mosseri, V., Ribeiro, A., Lequin, D., Vermeulen, J., Couturier, J., Peuchmaur, M. M., Valent, A., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.0630 · Cited by 350 · see citing works
Degradation of proteins by PROTACs and other strategies
Wang, Y., Jiang, X., Feng, F., Liu, W., & Sun, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.08.001 · Cited by 335 · see citing works
Exon Array Profiling Detects EML4-ALK Fusion in Breast, Colorectal, and Non–Small Cell Lung Cancers
Lin, E., Li, L., Guan, Y., Soriano, R. H., Rivers, C. S., Mohan, S., Pandita, A., Tang, J., & Modrusan, Z. D. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0522 · Cited by 298 · see citing works
Brouwer, S. D., Preter, K. D., Kumps, C., Zabrocki, P., Porcu, M., Westerhout, E. M., Lakeman, A., Vandesompele, J., Hoebeeck, J., Maerken, T. V., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2660 · Cited by 277 · see citing works
Kelly, L. M., Barila, G., Liu, P., Evdokimova, V. N., Trivedi, S., Panebianco, F., Gandhi, M., Carty, S. E., Hodak, S. P., Luo, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321937111 · Cited by 268 · see citing works
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 · see citing works
Renal cell carcinoma with novel VCL–ALK fusion: new representative of ALK-associated tumor spectrum
Debelenko, L. V., Raimondi, S. C., Daw, N. C., Shivakumar, B. R., Huang, D., Nelson, M., & Bridge, J. A. (2010) · Modern Pathology · doi:10.1038/modpathol.2010.213 · Cited by 245 · see citing works
Expression of the ALK Tyrosine Kinase Gene in Neuroblastoma
Lamant, L., Pulford, K. A. F., Bischof, D., Morris, S. W., Mason, D. Y., Delsol, G., & Mariamé, B. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65042-0 · Cited by 224 · see citing works
Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC)
Robb, C. M., Contreras, J. I., Kour, S., Taylor, M., Abid, M., Sonawane, Y. A., Zahid, M., Murry, D. J., Natarajan, A., & Rana, S. (2017) · Chemical Communications · doi:10.1039/c7cc03879h · Cited by 221 · see citing works
ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma
Paepe, P. D., Baens, M., van Krieken, J. H., Verhasselt, B., Stul, M. S., Simons, A., Poppe, B. G., Laureys, G., Brons, P., Vandenberghe, P., et al. (2003) · Blood · doi:10.1182/blood-2003-04-1050 · Cited by 190 · see citing works
Bilsland, J. G., Wheeldon, A., Mead, A., Znamenskiy, P., Almond, S., Waters, K. A., Thakur, M., Beaumont, V., Bonnert, T. P., Heavens, R., et al. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301446 · Cited by 188 · see citing works
Passoni, L., Longo, L., Collini, P., Coluccia, A. M. L., Bozzi, F., Podda, M. G., Gregorio, A., Gambini, C., Garaventa, A., Pistoia, V., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4419 · Cited by 171 · see citing works
ALK: a tyrosine kinase target for cancer therapyPreprint
Holla, V., Elamin, Y., Bailey, A. M., Johnson, A. M., Litzenburger, B., Khotskaya, Y., Sanchez, N. S., Zeng, J., Shufean, M. A., Shaw, K. R. M., et al. (2017) · Cold Spring Harbor molecular case studies · doi:10.1101/mcs.a001115 · Cited by 171 · see citing works
Increased ALK Gene Copy Number and Amplification are Frequent in Non-small Cell Lung Cancer
Salido, M., Pijuán, L., Martinez-Aviles, L. M., Galván, A. B., Cañadas, I., Rovira, A., Zanui, M., Martínez, A., Longarón, R., Solé, F. G., et al. (2010) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181fb7cd6 · Cited by 158 · see citing works
Liu, Z., Wakihara, T., Oshima, K., Nishioka, D., Hotta, Y., Elangovan, S. P., Yanaba, Y., Yoshikawa, T., Chaikittisilp, W., Matsuo, T., et al. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201501160 · Cited by 150 · see citing works
Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma
Du, X., Hu, H., Lin, D., Xia, S.-H., Shen, X., Zhang, Y., Luo, M., Feng, Y., Cai, Y., Xu, X., et al. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0159-4 · Cited by 133 · see citing works
Expression and functional analysis of the anaplastic lymphoma kinase (ALK) gene in tumor cell lines
Dirks, W. G., Fähnrich, S., Lis, Y., Becker, E., MacLeod, R. A. F., & Drexler, H. G. (2002) · International Journal of Cancer · doi:10.1002/ijc.10435 · Cited by 125 · see citing works
Demizu, Y., Shibata, N., Hattori, T., Ohoka, N., Motoi, H., Misawa, T., Shoda, T., Naito, M., & Kurihara, M. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.09.041 · Cited by 125 · see citing works
Identification of Anaplastic Lymphoma Kinase as a Potential Therapeutic Target in Ovarian Cancer
Ren, H., Tan, Z., Zhu, X., Crosby, K., Haack, H., Ren, J., Beausoleil, S. A., Moritz, A., Innocenti, G., Rush, A. J., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3931 · Cited by 123 · see citing works
Ceritinib in ALK-Rearranged Non–Small-Cell Lung Cancer
Shen, L., & Ji, H. (2014) · New England Journal of Medicine · doi:10.1056/nejmc1404894 · Cited by 118 · see citing works
Weiss, J. B., Xue, C., Benice, T. S., Xue, L., Morris, S. W., & Raber, J. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.10.024 · Cited by 109 · see citing works
Richards, M. W., O’Regan, L., Röth, D., Montgomery, J. M., Straube, A., Fry, A. M., & Bayliss, R. W. (2015) · Biochemical Journal · doi:10.1042/bj20150039 · Cited by 101 · see citing works
Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy
Ohoka, N., Shibata, N., Hattori, T., & Naito, M. (2016) · Current Cancer Drug Targets · doi:10.2174/1568009616666151112122502 · Cited by 55 · see citing works
Flagged first, then by citations
2 of the 57 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Small molecules in targeted cancer therapy: advances, challenges, and future perspectives
Zhong, L., Li, Y., Xiong, L., Wang, W., Wu, M., Yuan, T., Yang, W. M., Tian, C., Miao, Z., Wang, T., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00572-w · Cited by 1,735 · 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
Trends in kinase drug discovery: targets, indications and inhibitor design
Attwood, M. M., Fabbro, D., Sokolov, A. V., Knapp, S., & Schiöth, H. B. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00252-y · Cited by 807 · 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
Self-citationPROTACs: great opportunities for academia and industry
Sun, X., Gao, H., Yang, Y., He, M., Wu, Y., Song, Y.-G., Tong, Y., & Rao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0101-6 · Cited by 651 · 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
Proteolysis-targeting chimeras (PROTACs) in cancer therapy
Li, X., Pu, W., Zheng, Q., Ai, M., Chen, S., & Peng, Y. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01434-3 · Cited by 374 · see citing works
Zhang, L., Riley-Gillis, B., Vijay, P., & Shen, Y. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-1129 · Cited by 365 · see citing works
An, S., & Fu, L. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.09.005 · Cited by 363 · see citing works
Zoppi, 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 · see citing works
Degradation of proteins by PROTACs and other strategies
Wang, Y., Jiang, X., Feng, F., Liu, W., & Sun, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.08.001 · Cited by 335 · see citing works
Targeted protein degradation: advances in drug discovery and clinical practice
Zhong, G., Chang, X., Xie, W., & Zhou, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02004-x · Cited by 326 · see citing works
Quantitative Live-Cell Kinetic Degradation and Mechanistic Profiling of PROTAC Mode of Action
Riching, K. M., Mahan, S. D., Corona, C. R., McDougall, M. G., Vasta, J. D., Robers, M. B., Urh, M., & Daniels, D. L. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.8b00692 · Cited by 307 · see citing works
Cancer Selective Target Degradation by Folate-Caged PROTACs
Liu, J., Chen, H., Liu, Y., Shen, Y., Meng, F., Kanıskan, H. Ü., Jin, J. J., & Wei, W. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c00451 · Cited by 310 · see citing works
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Zou, Y., Ma, D., & Wang, Y. (2019) · Cell Biochemistry and Function · doi:10.1002/cbf.3369 · Cited by 307 · see citing works
Light-induced control of protein destruction by opto-PROTAC
Liu, J., Chen, H., Ma, L., He, Z., Wang, D., Liu, Y., Lin, Q., Zhang, T., Gray, N. S., Kanıskan, H. Ü., et al. (2020) · Science Advances · doi:10.1126/sciadv.aay5154 · Cited by 305 · see citing works
Self-citationTargeted protein degradation: A promise for undruggable proteins
Samarasinghe, K. T. G., & Crews, C. M. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.04.011 · Cited by 291 · see citing works
Hu, J., Hu, B., Wang, M., Xu, F., Miao, B., Yang, C., Wang, M., Liu, Z., Hayes, D. F., Chinnaswamy, K., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01572 · Cited by 286 · see citing works
Zeng, S., Huang, W., Zheng, X., Cheng, L., Zhang, Z., Wang, J., & Shen, Z. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112981 · Cited by 262 · see citing works
Cheng, M., Yu, X., Lu, K. J., Xie, L., Wang, L., Meng, F., Han, X., Chen, X., Liu, J., Xiong, Y., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01566 · Cited by 197 · see citing works
Self-citationALK-positive lung cancer: a moving target
Schneider, J. L., Lin, J. J., & Shaw, A. T. (2023) · Nature Cancer · doi:10.1038/s43018-023-00515-0 · Cited by 190 · see citing works
Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule
Zhao, Q., Lan, T., Su, S., & Rao, Y. (2018) · Chemical Communications · doi:10.1039/c8cc07813k · Cited by 185 · see citing works
Harnessing the Power of Proteolysis for Targeted Protein Inactivation
Verma, R., Mohl, D., & Deshaies, R. J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.01.010 · Cited by 185 · see citing works
PROTACs– a game-changing technology
Konstantinidou, M., Li, J., Zhang, B., Wang, Z., Shaabani, S., ter Brake, F., Essa, K., & Dömling, A. S. S. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1659242 · Cited by 167 · see citing works
Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta
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 · see citing works
Cereblon versus VHL: Hijacking E3 ligases against each other using PROTACs
Girardini, M., Maniaci, C., Hughes, S. J., Testa, A., & Ciulli, A. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.02.048 · Cited by 157 · 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
Developments of CRBN-based PROTACs as potential therapeutic agents
Wang, C., Zhang, Y., Wu, Y., & Xing, D. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113749 · Cited by 152 · see citing works
The peptide PROTAC modality: a novel strategy for targeted protein ubiquitination
Jin, J., Wu, Y., Chen, J., Shen, Y., Zhang, L., Zhang, H., Chen, L., Yuan, H., Chen, H., Zhang, W., et al. (2020) · Theranostics · doi:10.7150/thno.46985 · Cited by 146 · see citing works
Self-citationProteolysis-targeting chimeras with reduced off-targets
Nguyen, T. M., Sreekanth, V., Deb, A., Kokkonda, P., Tiwari, P. K., Donovan, K. A., Shoba, V. M., Chaudhary, S. K., Mercer, J. A. M., Lai, S., et al. (2023) · Nature Chemistry · doi:10.1038/s41557-023-01379-8 · Cited by 145 · see citing works
The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells
Kurimchak, A. M., Herrera-Montávez, C., Montserrat-Sangrà, S., Araiza-Olivera, D., Hu, J., Neumann-Domer, R., Kuruvilla, M., Bellacosa, A., Testa, J. R., Jin, J., et al. (2022) · Science Signaling · doi:10.1126/scisignal.abn2707 · Cited by 136 · see citing works
Self-citationDrug Discovery Targeting Anaplastic Lymphoma Kinase (ALK)
Kong, X., Pan, P., Sun, H., Xia, H., Wang, X., Li, Y., & Hou, T. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00446 · Cited by 134 · see citing works
Kang, C. H., Lee, D.-H., Lee, C. O., Ha, J. D., Park, C. H., & Hwang, J. Y. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.09.169 · Cited by 126 · see citing works
Chen, H., Liu, J., Kanıskan, H. Ü., Wei, W., & Jin, J. J. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00901 · Cited by 125 · see citing works
Self-citationProteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies
He, Y., Khan, S., Huo, Z., Lv, D., Zhang, X., Liu, X., Yuan, Y., Hromas, R., Xu, M., Zheng, G., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00924-z · Cited by 126 · see citing works
Bashraheel, S. S., Dömling, A. S. S., & Goda, S. K. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110009 · Cited by 122 · see citing works
Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update
Wu, T., Qin, Z., Tian, Y., Wang, J., Xu, C., Li, Z., & Bian, J. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00744 · Cited by 120 · see citing works
Bivalent Ligands for Protein Degradation in Drug Discovery
Scheepstra, M., Hekking, K. F. W., Hijfte, L. V., & Folmer, R. H. A. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.01.006 · Cited by 120 · see citing works
Strategies for designing proteolysis targeting chimaeras (PROTACs)
He, S., Dong, G., Cheng, J., Wu, Y., & Sheng, C. (2022) · Medicinal Research Reviews · doi:10.1002/med.21877 · Cited by 118 · see citing works
PROTAC’ing oncoproteins: targeted protein degradation for cancer therapy
Kelm, J. M., Pandey, D. S., Malin, E., Kansou, H. W., Arora, S., Kumar, R., & Gavande, N. S. (2023) · Molecular Cancer · doi:10.1186/s12943-022-01707-5 · Cited by 115 · see citing works
Plasticity in designing PROTACs for selective and potent degradation of HDAC6
Yang, H., Lv, W., He, M., Deng, H., Li, H., Wu, W., & Rao, Y. (2019) · Chemical Communications · doi:10.1039/c9cc08509b · Cited by 108 · see citing works
Discovery of First-in-Class Protein Arginine Methyltransferase 5 (PRMT5) Degraders
Shen, Y., Gao, G., Yu, X., Kim, H., Wang, L., Xie, L., Schwarz, M. C., Chen, X., Guccione, E., Liu, J., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01111 · Cited by 107 · see citing works
Self-citationDiscovery of potent small molecule PROTACs targeting mutant EGFR
Zhao, H., Yang, X., Lei, H., Xi, X.-X., Lu, S., Zhang, J., Xin, M., & Zhang, S. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112781 · Cited by 105 · see citing works
Self-citationBensimon, A., Pizzagalli, M. D., Kartnig, F., Dvorak, V., Essletzbichler, P., Winter, G. E., & Superti-Furga, G. (2020) · Cell Chemical Biology · doi:10.1016/j.chembiol.2020.04.003 · Cited by 102 · see citing works
Critical Assessment of Targeted Protein Degradation as a Research Tool and Pharmacological Modality
Kostić, M., & Jones, L. H. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.02.006 · Cited by 96 · see citing works
Novel immunomodulatory drugs and neo-substrates
Gao, S., Wang, S., & Song, Y. (2020) · Biomarker Research · doi:10.1186/s40364-020-0182-y · Cited by 95 · see citing works
Advances in targeted degradation of endogenous proteins
Röth, S., Fulcher, L. J., & Sapkota, G. P. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03112-6 · Cited by 92 · see citing works
Cao, C.-G., Yang, J., Chen, Y. X., Zhou, P., Wang, Y., Du, W., Zhao, L., & Chen, Y. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00821 · Cited by 90 · see citing works
PROTAC therapy as a new targeted therapy for lung cancer
Li, J. W., Zheng, G., Kaye, F. J., & Wu, L. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2022.11.011 · Cited by 87 · see citing works
Stimuli-activatable PROTACs for precise protein degradation and cancer therapy
Gao, J., Yang, L., Lei, S., Zhou, F., Nie, H., Peng, B., Xu, T., Chen, X., Yang, X., Sheng, C., et al. (2023) · 中国科学通报：英文版 · doi:10.1016/j.scib.2023.04.028 · Cited by 87 · see citing works
Self-citationPiperlongumine conjugates induce targeted protein degradation
Pei, J., Xiao, Y., Liu, X., Hu, W., Sobh, A., Yuan, Y., Zhou, S., Hua, N., Mackintosh, S. G., Zhang, X., et al. (2023) · Cell chemical biology · doi:10.1016/j.chembiol.2023.01.004 · Cited by 84 · see citing works
Sun, N., Ren, C., Kong, Y., Zhong, H., Chen, J., Li, Y., Zhang, J., Zhou, Y., Qiu, X., Lin, H., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112190 · Cited by 85 · see citing works
Self-citationWang, Y., Han, L., Liu, F., Yang, F., Jiang, X., Sun, H., Feng, F., Xue, J., & Liu, W. (2020) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2020.110795 · Cited by 82 · see citing works
Chemoselective Synthesis of Lenalidomide-Based PROTAC Library Using Alkylation Reaction
Qiu, X., Sun, N., Kong, Y., Li, Y., Yang, X., & Jiang, B. (2019) · Organic Letters · doi:10.1021/acs.orglett.9b01326 · Cited by 81 · see citing works
Self-citationDevelopment of Alectinib-Based PROTACs as Novel Potent Degraders of Anaplastic Lymphoma Kinase (ALK)
Xie, S., Sun, Y., Liu, Y., Li, X., Li, X., Zhong, W., Zhan, F., Zhu, J., Yao, H., Yang, D., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00270 · Cited by 81 · see citing works
Distinct CDK6 complexes determine tumor cell response to CDK4/6 inhibitors and degraders
Wu, X., Yang, X., Xiong, Y., Li, R., Ito, T., Ahmed, T. A., Karoulia, Z., Adamopoulos, C., Wang, H., Wang, L., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00174-z · Cited by 74 · see citing works
Self-citationDesigning Chimeric Molecules for Drug Discovery by Leveraging Chemical Biology
Borsari, C., Trader, D. J., Tait, A., & Costi, M. P. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01456 · Cited by 75 · see citing works
Chen, S., Cui, J., Chen, H., Yu, B., & Long, S. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115911 · Cited by 70 · see citing works
Evolution of Cereblon-Mediated Protein Degradation as a Therapeutic Modality
Chamberlain, P. P., D’Agostino, L. A., Ellis, J. M., Hansen, J. D., Matyskiela, M. E., McDonald, J. J., Riggs, J. R., & Hamann, L. G. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.9b00425 · Cited by 69 · see citing works
Yang, L., Tu, W., Huang, L., Miao, B., Kaneshige, A., Jiang, W., Leng, L., Wang, M., Wen, B., Sun, D., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00953 · Cited by 69 · see citing works
Targeting ALK Rearrangements in NSCLC: Current State of the Art
Peng, L., Zhu, L., Sun, Y., Stebbing, J., Selvaggi, G., Zhang, Y., & Yu, Z. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.863461 · Cited by 71 · see citing works
Monitoring and deciphering protein degradation pathways inside cells
Daniels, D. L., Riching, K. M., & Urh, M. (2018) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2018.12.001 · Cited by 68 · see citing works
Discovery of a First-in-Class Mitogen-Activated Protein Kinase Kinase 1/2 Degrader
Wei, J., Hu, J., Wang, L., Xie, L., Jin, M. S., Chen, X., Liu, J., & Jin, J. J. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01528 · Cited by 67 · see citing works
Self-citationSmall molecule PROTACs: an emerging technology for targeted therapy in drug discovery
Pei, H., Peng, Y., Zhao, Q., & Chen, Y. (2019) · RSC Advances · doi:10.1039/c9ra03423d · Cited by 65 · see citing works
Discovery of Selective Small Molecule Degraders of BRAF-V600E
Han, X., Chen, L., Wei, Y., Yu, W., Chen, Y., Zhang, C., Jiao, B., Shi, T., Sun, L., Zhang, C., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b02083 · Cited by 64 · see citing works
Self-citationProteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future
Li, R., Liu, M., Yang, Z., Li, J., Gao, Y., & Tan, R. (2022) · Molecules · doi:10.3390/molecules27248828 · Cited by 64 · see citing works
Shagufta, Ahmad, I., Mathew, S., & Rahman, S. (2020) · RSC Medicinal Chemistry · doi:10.1039/c9md00570f · Cited by 64 · see citing works
Li, M., Yang, Y., Zhao, Q., Wu, Y., Song, L., Yang, H., He, M., Gao, H., Song, B., Luo, J., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00339 · Cited by 64 · see citing works
Update on the Development of MNK Inhibitors as Therapeutic Agents
Xu, W., Kannan, S., Verma, C. S., & Nacro, K. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00368 · Cited by 61 · see citing works
Journey of PROTAC: From Bench to Clinical Trial and Beyond
Berkley, K., Zalejski, J., Sharma, N., & Sharma, A. K. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00577 · Cited by 62 · see citing works
Novel targeted therapies of T cell lymphomas
Iżykowska, K., Rassek, K., Korsak, D., & Przybylski, G. K. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-01006-w · Cited by 60 · see citing works
Targeted degradation of extracellular secreted and membrane proteins
Chen, X., Zhou, Y., Zhao, Y., & Tang, W. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.08.013 · Cited by 59 · see citing works
Discovery of a PROTAC targeting ALK with in vivo activity
Yan, G., Zhong, X.-X., Lin, Y., Pu, C., Shan, H., Lan, S., Zhou, M., Hou, X., Yang, J., & Li, R. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.113150 · Cited by 59 · see citing works
Enriching Proteolysis Targeting Chimeras with a Second Modality: When Two Are Better Than One
Salerno, A., Seghetti, F., Caciolla, J., Uliassi, E., Testi, E., Guardigni, M., Roberti, M., Milelli, A., & Bolognesi, M. L. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00302 · Cited by 55 · see citing works
Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation
Xi, M., Chen, Y., Yang, H., Xu, H., Du, K., Wu, C., Xu, Y., Deng, L., Luo, X., Yu, L., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.04.036 · Cited by 56 · see citing works
Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders
Chen, L., Chen, Y., Zhang, C., Jiao, B., Liang, S., Qiong, T., Chai, H., Yu, W., Qian, Y., Yang, H., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01342 · Cited by 55 · see citing works
Self-citationA 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
Desai, A. P., & Lovly, C. M. (2023) · Translational Lung Cancer Research · doi:10.21037/tlcr-22-708 · Cited by 52 · see citing works
Catalytic Degraders Effectively Address Kinase Site Mutations in EML4-ALK Oncogenic Fusions
Gao, Y., Jiang, B., Kim, H., Berberich, M. J., Che, J., Donovan, K. A., Hatcher, J. M., Huerta, F., Kwiatkowski, N. P., Liu, Y., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01864 · Cited by 50 · see citing works
Self-citationProteolysis Targeting Chimeras (PROTACs): A Perspective on Integral Membrane Protein Degradation
Ruffilli, C., Röth, S., Rodrigo, M., Boyd, H., Zelcer, N., & Moreau, K. (2022) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.2c00142 · Cited by 50 · see citing works
Ren, C., Sun, N., Kong, Y., Qu, X., Liu, H., Zhong, H., Song, X., Yang, X., & Jiang, B. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113335 · Cited by 49 · see citing works
Self-citationResearch progress of MEK1/2 inhibitors and degraders in the treatment of cancer
Wang, C., Wang, H., Zheng, C., Liu, Z., Gao, X., Xu, F., Niu, Y., Zhang, L., & Xu, P. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113386 · Cited by 49 · see citing works
Maksoud, S. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02339-4 · Cited by 48 · see citing works
Song, X., Zhong, H., Qu, X., Yang, L., & Jiang, B. (2021) · MedComm · doi:10.1002/mco2.42 · Cited by 48 · see citing works
Self-citationVenkatesan, J., Murugan, D., Lakshminarayanan, K., Smith, A. R., Thirumalaiswamy, H. V., Kandhasamy, H., Zender, B., Zheng, G., & Rangasamy, L. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108725 · Cited by 47 · see citing works
Multi-therapies Based on PARP Inhibition: Potential Therapeutic Approaches for Cancer Treatment
Zhang, J., Gao, Y., Zhang, Z., Zhao, J., Jia, W., Xia, C., Wang, F., & Liu, T. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01352 · Cited by 46 · see citing works
Identification of probe-quality degraders for Poly(ADP-ribose) polymerase-1 (PARP-1)
Zhang, Z., Chang, X., Zhang, C., Zeng, S., Liang, M., Ma, Z., Wang, Z., Huang, W., & Shen, Z. (2020) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2020.1804382 · Cited by 46 · see citing works
Self-citationChemically Induced Cellular Proteolysis: An Emerging Therapeutic Strategy for Undruggable Targets.
Moon, S., & Lee, B. (2018) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2018.0372 · Cited by 45 · see citing works
Proteases and Their Modulators in Cancer Therapy: Challenges and Opportunities
Song, R., Qiao, W., He, J., Huang, J., Luo, Y., & Yang, T. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01640 · Cited by 45 · see citing works
Homobivalent, Trivalent, and Covalent PROTACs: Emerging Strategies for Protein Degradation
Yan, J., Li, T., Miao, Z., Wang, P., Sheng, C., & Zhuang, C. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00728 · Cited by 44 · see citing works
Hu, J., Wei, J., Yim, H., Wang, L., Xie, L., Jin, M. S., Kabir, M., Qin, L., Chen, X., Liu, J., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01609 · Cited by 43 · see citing works
Self-citationYu, X., Xu, J., Shen, Y., Cahuzac, K. M., Park, K., Dale, B., Liu, J., Parsons, R. E., & Jin, J. J. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c02165 · Cited by 43 · see citing works
Self-citationDegraders in epigenetic therapy: PROTACs and beyond
Dai, X., Ji, S., Fu, M., Liu, G.-Z., Liu, H., Wang, S., Shen, L., Wang, N., Herdewijn, P. A., Zheng, Y., et al. (2024) · Theranostics · doi:10.7150/thno.92526 · Cited by 44 · see citing works
Induced proximity-based therapeutic modalities
King, E. A., Meyers, M., & Nomura, D. K. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01316-z · Cited by 42 · see citing works
Aboelez, M. O., Belal, A., Xiang, G., & Ma, X. (2022) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2022.2062338 · Cited by 41 · see citing works
Cereblon-Recruiting PROTACs: Will New Drugs Have to Face Old Challenges?
Cieślak, M., & Słowianek, M. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15030812 · Cited by 41 · see citing works
ALK in cancer: from function to therapeutic targeting
Voena, C., Ambrogio, C., Iannelli, F., & Chiarle, R. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00797-9 · Cited by 45 · see citing works
Ren, C., Sun, N., Liu, H., Kong, Y., Sun, R., Qiu, X., Chen, J., Li, Y., Zhang, J., Zhou, Y., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00373 · Cited by 41 · see citing works
Self-citationManeiro, M., Vita, E. D., Conole, D., Kounde, C. S., Zhang, Q., & Tate, E. W. (2021) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2021.01.002 · Cited by 38 · see citing works
Light-Controllable PROTACs for Temporospatial Control of Protein Degradation
Liu, J., Peng, Y., & Wei, W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.678077 · Cited by 38 · see citing works
Self-citation
- Authors
- Zhang, C., Han, X.-R., Yang, X., Jiang, B., Liu, J., Xiong, Y., & Jin, J.
- Affiliations
- Tisch Cancer Institute (US)
- ShanghaiTech University (CN)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Liu, Jing
- Xiong, Yue
- Jin, Jian
- Venue
- European Journal of Medicinal Chemistry
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 151
- Pages
- 304-314
- ISSN
- 0223-5234 (ISSN-L)
- PMC
- PMC5924614
- OpenAlex
- W2794623623
- Cited by
- 226
- References
- 57
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 24 · 2023: 26 · 2022: 31 · 2021: 31 · 2020: 38 · 2019: 26 · 2018: 9 · 2014: 1
- FWCI
- 9.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U. S. National Institutes of Health (R01GM067113)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- PROTACs, anaplastic lymphoma kinase, cereblon ligands, proteasomal degradation, ALK fusion proteins, drug resistance, non-small cell lung cancer, ALK-positive lymphoma, pharmacokinetics, kinase inhibitors
- MeSH terms
- Anaplastic Lymphoma Kinase, Animals, Antineoplastic Agents, Humans, Lung Neoplasms, Lymphoma, Male, Drug Design, Signal Transduction, Receptor Protein-Tyrosine Kinases, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation, Mice, Proteolysis
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