Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Recent Advances in the Design and Development of Anticancer Molecules based on PROTAC Technology

Author(s): Zere Mukhamejanova, Yichen Tong , Qi Xiang, Fang Xu* and Jiyan Pang*

Volume 28, Issue 7, 2021

Published on: 12 March, 2020

Page: [1304 - 1327] Pages: 24

DOI: 10.2174/0929867327666200312112412

Price: $65

Abstract

PROTAC (Proteolysis Targeting Chimera) degraders based on protein knockdown technology are now suggested as a novel option for the treatment of various diseases. Over the last couple of years, the application of PROTAC technology has spread in a wide range of disorders, and plenty of PROTAC molecules with high potency have been reported. Mostly developing for anticancer therapy, these molecules showed high selectivities to target proteins, the ability to significantly induce degradation of oncoproteins, good in vitro and in vivo results. In this review, we summarized the recent development of PROTAC technology in the anticancer therapy field, including molecular design, types of targeted proteins, in vitro and in vivo results. Additionally, we also discuss the prospects and challenges for the application of candidates based on PROTAC strategy in clinical trials.

Keywords: PROTAC, Small molecule degrader, targeted protein degradation, anticancer therapy, molecular design, diseases.

« Previous Next »
[1]
Cong, L.; Ran, F.A.; Cox, D.; Lin, S.; Barretto, R.; Habib, N.; Hsu, P.D.; Wu, X.; Jiang, W.; Marraffini, L.A.; Zhang, F. Multiplex genome engineering using CRISPR/Cas systems. Science, 2013, 339(6121), 819-823.
[http://dx.doi.org/10.1126/science.1231143] [PMID: 23287718]
[2]
Ohba, H.; Zhelev, Z.; Bakalova, R.; Ewis, A.; Omori, T.; Ishikawa, M.; Shinohara, Y.; Baba, Y. Inhibition of bcr-abl and/or c-abl gene expression by small interfering, double-stranded RNAs: cross-talk with cell proliferation factors and other oncogenes. Cancer, 2004, 101(6), 1390-1403.
[http://dx.doi.org/10.1002/cncr.20468] [PMID: 15368327]
[3]
Burnett, J.C.; Rossi, J.J. RNA-based therapeutics: current progress and future prospects. Chem. Biol., 2012, 19(1), 60-71.
[http://dx.doi.org/10.1016/j.chembiol.2011.12.008] [PMID: 22284355]
[4]
Pei, H.; Peng, Y.; Zhao, Q.; Chen, Y. Small molecule PROTACs: an emerging technology for targeted therapy in drug discovery. RSC Adv, 2019, 9(30), 16967-16976.
[http://dx.doi.org/10.1039/C9RA03423D]]
[5]
Raina, K.; Lu, J.; Qian, Y.; Altieri, M.; Gordon, D.; Rossi, A.M.; Wang, J.; Chen, X.; Dong, H.; Siu, K.; Winkler, J.D.; Crew, A.P.; Crews, C.M.; Coleman, K.G. PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. Proc. Natl. Acad. Sci. USA, 2016, 113(26), 7124-7129.
[http://dx.doi.org/10.1073/pnas.1521738113]] [PMID: 27274052]
[6]
Neklesa, T.; Snyder, L.B.; Willard, R.R.; Vitale, N.; Raina, K.; Pizzano, J.; Gordon, D.; Bookbinder, M.; Macaluso, J.; Dong, H.; Liu, Z.; Ferraro, C.; Wang, G.; Wang, J.; Crews, C.M.; Houston, J.; Crews, P.C.; Taylor, I. Abstract 5236: ARV-110: an androgen receptor PROTAC degrader for prostate cancer. Cancer Res., 2018, 78(13), 5236.
[http://dx.doi.org/10.1158/1538-7445.AM2018-5236]]
[7]
Flanagan, J.J.; Qian, Y.; Gough, S.M.; Andreoli, M.; Bookbinder, M.; Cadelina, G.; Bradley, J.; Rousseau, E.; Willard, R.; Pizzano, J.; Crews, C.M. Abstract P5-04-18: ARV-471, an oral estrogen receptor PROTAC degrader for breast cancer. Cancer Res 2019, 79(Suppl. 4), P5-04-18,
[http://dx.doi.org/10.1158/1538-7445.SABCS18-P5-04-18]
[8]
Kelleher, J.; Campbell, V.; Chen, J.; Gollob, J.; Ji, N.; Kamadurai, H.; Klaus, C.; Li, H.; Loh, C.; McDonald, A.; Rong, H.; Rusin, S.; Sharma, K.; Vigil, D.; Walker, D.; Weiss, M.; Yuan, K.; Zhang, Y.; Mainolfi, N. KYM-001, a first-in-class oral IRAK4 protein degrader, induces tumor regression in xenograft models of MYD88-mutant ABC DLBCL alone and in combination with BTK inhibition. Hematol. Oncol., 2019, 37(S2), 129-129.
[http://dx.doi.org/10.1002/hon.89_2629]]
[9]
Mofers, A.; Pellegrini, P.; Linder, S.; D’Arcy, P. Proteasome-associated deubiquitinases and cancer. Cancer Metastasis Rev., 2017, 36(4), 635-653.
[http://dx.doi.org/10.1007/s10555-017-9697-6] [PMID: 29134486]
[10]
Warang, P.; Homma, T.; Pandya, R.; Sawant, A.; Shinde, N.; Pandey, D.; Fujii, J.; Madkaikar, M.; Mukherjee, M.B. Potential involvement of ubiquitin-proteasome system dysfunction associated with oxidative stress in the pathogenesis of sickle cell disease. Br. J. Haematol., 2018, 182(4), 559-566.
[http://dx.doi.org/10.1111/bjh.15437] [PMID: 29974957]
[11]
Schwartz, A.L.; Ciechanover, A. Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annu. Rev. Pharmacol. Toxicol., 2009, 49, 73-96.
[http://dx.doi.org/10.1146/annurev.pharmtox.051208.165340] [PMID: 18834306]
[12]
Hershko, A.; Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem., 1998, 67(1), 425-479.
[http://dx.doi.org/10.1146/annurev.biochem.67.1.425] [PMID: 9759494]
[13]
Tramutola, A.; Di Domenico, F.; Barone, E.; Perluigi, M.; Butterfield, D.A. It is all about (U)biquitin: role of altered ubiquitin-proteasome system and UCHL1 in Alzheimer disease. Oxid. Med. Cell. Longev., 2016, 20162756068
[http://dx.doi.org/10.1155/2016/2756068] [PMID: 26881020]
[14]
Sakamoto, K.M.; Kim, K.B.; Kumagai, A.; Mercurio, F.; Crews, C.M.; Deshaies, R.J. Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. Proc. Natl. Acad. Sci. USA, 2001, 98(15), 8554-8559.
[http://dx.doi.org/10.1073/pnas.141230798] [PMID: 11438690]
[15]
Sakamoto, K.M.; Kim, K.B.; Verma, R.; Ransick, A.; Stein, B.; Crews, C.M.; Deshaies, R.J. Development of PROTACs to target cancer-promoting proteins for ubiquitination and degradation. Mol. Cell. Proteomics, 2003, 2(12), 1350-1358.
[http://dx.doi.org/10.1074/mcp.T300009-MCP200] [PMID: 14525958]
[16]
Schapira, M.; Calabrese, M.F.; Bullock, A.N.; Crews, C.M. Targeted protein degradation: expanding the toolbox. Nat. Rev. Drug Discov., 2019, 18(12), 949-963.
[http://dx.doi.org/10.1038/s41573-019-0047-y] [PMID: 31666732]
[17]
Shi, Y.; Long, M.J.C.; Rosenberg, M.M.; Li, S.; Kobjack, A.; Lessans, P.; Coffey, R.T.; Hedstrom, L. Boc3Arg-linked ligands induce degradation by localizing target proteins to the 20S proteasome. ACS Chem. Biol., 2016, 11(12), 3328-3337.
[http://dx.doi.org/10.1021/acschembio.6b00656] [PMID: 27704767]
[18]
Gustafson, J.L.; Neklesa, T.K.; Cox, C.S.; Roth, A.G.; Buckley, D.L.; Tae, H.S.; Sundberg, T.B.; Stagg, D.B.; Hines, J.; McDonnell, D.P.; Norris, J.D.; Crews, C.M. Small-molecule-mediated degradation of the androgen receptor through hydrophobic tagging. Angew. Chem. Int. Ed. Engl., 2015, 54(33), 9659-9662.
[http://dx.doi.org/10.1002/anie.201503720] [PMID: 26083457]
[19]
Neklesa, T.K.; Winkler, J.D.; Crews, C.M. Targeted protein degradation by PROTACs. Pharmacol. Ther., 2017, 174, 138-144.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.027] [PMID: 28223226]
[20]
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. Lessons in PROTAC design from selective degradation with a promiscuous warhead. Cell Chem. Biol., 2018, 25(1), 78.e5-87.e5.
[http://dx.doi.org/10.1016/j.chembiol.2017.09.010] [PMID: 29129718]
[21]
Riching, K.M.; Mahan, S.; Corona, C.R.; McDougall, M.; Vasta, J.D.; Robers, M.B.; Urh, M.; Daniels, D.L. Quantitative live-cell kinetic degradation and mechanistic profiling of PROTAC mode of action. ACS Chem. Biol., 2018, 13(9), 2758-2770.
[http://dx.doi.org/10.1021/acschembio.8b00692] [PMID: 30137962]
[22]
Lai, A.C.; Crews, C.M. Induced protein degradation: an emerging drug discovery paradigm. Nat. Rev. Drug Discov., 2017, 16(2), 101-114.
[http://dx.doi.org/10.1038/nrd.2016.211] [PMID: 27885283]
[23]
Zou, Y.; Ma, D.; Wang, Y. The PROTAC technology in drug development. Cell Biochem. Funct., 2019, 37(1), 21-30.
[http://dx.doi.org/10.1002/cbf.3369] [PMID: 30604499]
[24]
Pettersson, M.; Crews, C.M. Proteolysis targeting chimeras (PROTACs) - past, present and future. Drug Discov. Today. Technol., 2019, 31, 15-27.
[http://dx.doi.org/10.1016/j.ddtec.2019.01.002] [PMID: 31200855]
[25]
Tan, L.; Gray, N.S. When kinases meet PROTACs. Chin. J. Chem., 2018, 36(10), 971-977.
[http://dx.doi.org/10.1002/cjoc.201800293]
[26]
Scheepstra, M.; Hekking, K.F.W.; van Hijfte, L.; Folmer, R.H.A. Bivalent ligands for protein degradation in drug discovery. Comput. Struct. Biotechnol. J., 2019, 17, 160-176.
[http://dx.doi.org/10.1016/j.csbj.2019.01.006] [PMID: 30788082]
[27]
Hines, J.; Gough, J.D.; Corson, T.W.; Crews, C.M. Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs. Proc. Natl. Acad. Sci. USA, 2013, 110(22), 8942-8947.
[http://dx.doi.org/10.1073/pnas.1217206110] [PMID: 23674677]
[28]
Reynders, M.; Matsuura, B.; Berouti, M.; Simoneschi, D.; Marzio, A.; Pagano, M.; Trauner, D. PHOTACs enable optical control of protein degradation. Sci. Adv., 2020, 6(8)eaay5064
[http://dx.doi.org/10.1126/sciadv.aay5064]] [PMID: 32128406]
[29]
Xue, G.; Wang, K.; Zhou, D.; Zhong, H.; Pan, Z. Light-induced protein degradation with photocaged PROTACs. J. Am. Chem. Soc., 2019, 141(46), 18370-18374.
[http://dx.doi.org/10.1021/jacs.9b06422] [PMID: 31566962]
[30]
Steinebach, C.; Lindner, S.; Udeshi, N.D.; Mani, D.C.; Kehm, H.; Köpff, S.; Carr, S.A.; Gütschow, M.; Krönke, J. Homo-PROTACs for the chemical knockdown of cereblon. ACS Chem. Biol., 2018, 13(9), 2771-2782.
[http://dx.doi.org/10.1021/acschembio.8b00693] [PMID: 30118587]
[31]
Maniaci, C.; Hughes, S.J.; Testa, A.; Chen, W.; Lamont, D.J.; Rocha, S.; Alessi, D.R.; Romeo, R.; Ciulli, A. Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation. Nat. Commun., 2017, 8(1), 830.
[http://dx.doi.org/10.1038/s41467-017-00954-1] [PMID: 29018234]
[32]
Girardini, M.; Maniaci, C.; Hughes, S.J.; Testa, A.; Ciulli, A. Cereblon versus VHL: hijacking E3 ligases against each other using PROTACs. Bioorg. Med. Chem., 2019, 27(12), 2466-2479.
[http://dx.doi.org/10.1016/j.bmc.2019.02.048] [PMID: 30826187]
[33]
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.; Scott, T.G.; Vittori, S.; Perry, J.A.; Qi, J.; Winter, G.E.; Wong, K.K.; Gray, N.S.; Bradner, J.E. The dTAG system for immediate and target-specific protein degradation. Nat. Chem. Biol., 2018, 14(5), 431-441.
[http://dx.doi.org/10.1038/s41589-018-0021-8] [PMID: 29581585]
[34]
Nalawansha, D.A.; Paiva, S.L.; Rafizadeh, D.N.; Pettersson, M.; Qin, L.; Crews, C.M. Targeted protein internalization and degradation by endosome targeting chimeras (ENDTACs). ACS Cent. Sci., 2019, 5(6), 1079-1084.
[http://dx.doi.org/10.1021/acscentsci.9b00224] [PMID: 31263767]
[35]
Banik, S.M.; Pedram, K.; Wisnovsky, S.; Ahn, G.; Riley, N.M.; Bertozzi, C.R. Lysosometargeting chimeras (LYTACs) for the degradation of secreted and membraneproteins. Nature, 2020, 584(7820), 291-297.
[http://dx.doi.org/10.1038/s41586-020-2545-9] [PMID: 32728216]
[36]
Lebraud, H.; Wright, D.J.; Johnson, C.N.; Heightman, T.D. Protein degradation by in-cell self-assembly of proteolysis targeting chimeras. ACS Cent. Sci., 2016, 2(12), 927-934.
[http://dx.doi.org/10.1021/acscentsci.6b00280] [PMID: 28058282]
[37]
Rodriguez-Gonzalez, A.; Cyrus, K.; Salcius, M.; Kim, K.; Crews, C.M.; Deshaies, R.J.; Sakamoto, K.M. Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer. Oncogene, 2008, 27(57), 7201-7211.
[http://dx.doi.org/10.1038/onc.2008.320] [PMID: 18794799]
[38]
Cyrus, K.; Wehenkel, M.; Choi, E.Y.; Lee, H.; Swanson, H.; Kim, K.B. Jostling for position: optimizing linker location in the design of estrogen receptor-targeting PROTACs. ChemMedChem, 2010, 5(7), 979-985.
[http://dx.doi.org/10.1002/cmdc.201000146] [PMID: 20512796]
[39]
Jiang, Y.; Deng, Q.; Zhao, H.; Xie, M.; Chen, L.; Yin, F.; Qin, X.; Zheng, W.; Zhao, Y.; Li, Z. Development of stabilized peptide-based PROTACs against estrogen receptor alpha. ACS Chem. Biol., 2018, 13(3), 628-635.
[http://dx.doi.org/10.1021/acschembio.7b00985] [PMID: 29271628]
[40]
Itoh, Y.; Kitaguchi, R.; Ishikawa, M.; Naito, M.; Hashimoto, Y. Design, synthesis and biological evaluation of nuclear receptor-degradation inducers. Bioorg. Med. Chem., 2011, 19(22), 6768-6778.
[http://dx.doi.org/10.1016/j.bmc.2011.09.041] [PMID: 22014751]
[41]
Narayanan, R.; Ponnusamy, S.; Miller, D.D. Destroying the androgen receptor (AR)-potential strategy to treat advanced prostate cancer. Oncoscience, 2017, 4(11-12), 175-177.
[http://dx.doi.org/10.18632/oncoscience.389] [PMID: 29344555]
[42]
Crowder, C.M.; Lassiter, C.S.; Gorelick, D.A. Nuclear androgen receptor regulates testes organization and oocyte maturation in zebrafish. Endocrinology, 2018, 159(2), 980-993.
[http://dx.doi.org/10.1210/en.2017-00617] [PMID: 29272351]
[43]
Flanagan, J.J.; Neklesa, T.K. Targeting nuclear receptors with PROTAC degraders. Mol. Cell. Endocrinol., 2019, 493110452
[http://dx.doi.org/10.1016/j.mce.2019.110452] [PMID: 31125586]
[44]
Schneekloth, A.R.; Pucheault, M.; Tae, H.S.; Crews, C.M. Targeted intracellular protein degradation induced by a small molecule: en route to chemical proteomics. Bioorg. Med. Chem. Lett., 2008, 18(22), 5904-5908.
[http://dx.doi.org/10.1016/j.bmcl.2008.07.114] [PMID: 18752944]
[45]
Shibata, N.; Nagai, K.; Morita, Y.; Ujikawa, O.; Ohoka, N.; Hattori, T.; Koyama, R.; Sano, O.; Imaeda, Y.; Nara, H.; Cho, N.; Naito, M. Development of protein degradation inducers of androgen receptor by conjugation of androgen receptor ligands and inhibitor of apoptosis protein ligands. J. Med. Chem., 2018, 61(2), 543-575.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00168] [PMID: 28594553]
[46]
Salami, J.; Alabi, S.; Willard, R.R.; Vitale, N.J.; Wang, J.; Dong, H.; Jin, M.; McDonnell, D.P.; Crew, A.P.; Neklesa, T.K.; Crews, C.M. Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance. Commun. Biol., 2018, 1(1), 100.
[http://dx.doi.org/10.1038/s42003-018-0105-8] [PMID: 30271980]
[47]
Han, X.; Wang, C.; Qin, C.; Xiang, W.; Fernandez-Salas, E.; Yang, C.Y.; Wang, M.; Zhao, L.; Xu, T.; Chinnaswamy, K.; Delproposto, J.; Stuckey, J.; Wang, S. Discovery of ARD-69 as a highly potent proteolysis targeting chimera (PROTAC) degrader of androgen receptor (AR) for the treatment of prostate cancer. J. Med. Chem., 2019, 62(2), 941-964.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01631] [PMID: 30629437]
[48]
Han, X.; Zhao, L.; Xiang, W.; Qin, C.; Miao, B.; Xu, T.; Wang, M.; Yang, C.Y.; Chinnaswamy, K.; Stuckey, J.; Wang, S. Discovery of highly potent and efficient PROTAC degraders of androgen receptor (AR) by employing weak binding affinity VHL E3 ligase ligands. J. Med. Chem., 2019, 62(24), 11218-11231.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01393] [PMID: 31804827]
[49]
Nadji, M.; Gomez-Fernandez, C.; Ganjei-Azar, P.; Morales, A.R. Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5,993 breast cancers. Am. J. Clin. Pathol., 2005, 123(1), 21-27.
[http://dx.doi.org/10.1309/4WV79N2GHJ3X1841] [PMID: 15762276]
[50]
Demizu, Y.; Okuhira, K.; Motoi, H.; Ohno, A.; Shoda, T.; Fukuhara, K.; Okuda, H.; Naito, M.; Kurihara, M. Design and synthesis of estrogen receptor degradation inducer based on a protein knockdown strategy. Bioorg. Med. Chem. Lett., 2012, 22(4), 1793-1796.
[http://dx.doi.org/10.1016/j.bmcl.2011.11.086] [PMID: 22277276]
[51]
Okuhira, K.; Demizu, Y.; Hattori, T.; Ohoka, N.; Shibata, N.; Nishimaki-Mogami, T.; Okuda, H.; Kurihara, M.; Naito, M. Development of hybrid small molecules that induce degradation of estrogen receptor-alpha and necrotic cell death in breast cancer cells. Cancer Sci., 2013, 104(11), 1492-1498.
[http://dx.doi.org/10.1111/cas.12272] [PMID: 23992566]
[52]
Ohoka, N.; Okuhira, K.; Ito, M.; Nagai, K.; Shibata, N.; Hattori, T.; Ujikawa, O.; Shimokawa, K.; Sano, O.; Koyama, R.; Fujita, H.; Teratani, M.; Matsumoto, H.; Imaeda, Y.; Nara, H.; Cho, N.; Naito, M. In vivo knockdown of pathogenic proteins via specific and nongenetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs). J. Biol. Chem., 2017, 292(11), 4556-4570.
[http://dx.doi.org/10.1074/jbc.M116.768853] [PMID: 28154167]
[53]
Ohoka, N.; Morita, Y.; Nagai, K.; Shimokawa, K.; Ujikawa, O.; Fujimori, I.; Ito, M.; Hayase, Y.; Okuhira, K.; Shibata, N.; Hattori, T.; Sameshima, T.; Sano, O.; Koyama, R.; Imaeda, Y.; Nara, H.; Cho, N.; Naito, M. Derivatization of inhibitor of apoptosis protein (IAP) ligands yields improved inducers of estrogen receptor α degradation. J. Biol. Chem., 2018, 293(18), 6776-6790.
[http://dx.doi.org/10.1074/jbc.RA117.001091] [PMID: 29545311]
[54]
Hu, J.; Hu, B.; Wang, M.; Xu, F.; Miao, B.; Yang, C.Y.; Wang, M.; Liu, Z.; Hayes, D.F.; Chinnaswamy, K.; Delproposto, J.; Stuckey, J.; Wang, S. Discovery of ERD-308 as a highly potent proteolysis targeting chimera (PROTAC) degrader of estrogen receptor (ER). J. Med. Chem., 2019, 62(3), 1420-1442.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01572] [PMID: 30990042]
[55]
Burris, T.P.; Busby, S.A.; Griffin, P.R. Targeting orphan nuclear receptors for treatment of metabolic diseases and autoimmunity. Chem. Biol., 2012, 19(1), 51-59.
[http://dx.doi.org/10.1016/j.chembiol.2011.12.011] [PMID: 22284354]
[56]
Bondeson, D.P.; Mares, A.; Smith, I.E.; Ko, E.; Campos, S.; Miah, A.H.; Mulholland, K.E.; Routly, N.; Buckley, D.L.; Gustafson, J.L.; Zinn, N.; Grandi, P.; Shimamura, S.; Bergamini, G.; Faelth-Savitski, M.; Bantscheff, M.; Cox, C.; Gordon, D.A.; Willard, R.R.; Flanagan, J.J.; Casillas, L.N.; Votta, B.J.; den Besten, W.; Famm, K.; Kruidenier, L.; Carter, P.S.; Harling, J.D.; Churcher, I.; Crews, C.M. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat. Chem. Biol., 2015, 11(8), 611-617.
[http://dx.doi.org/10.1038/nchembio.1858] [PMID: 26075522]
[57]
Peng, L.; Zhang, Z.; Lei, C.; Li, S.; Zhang, Z.; Ren, X.; Chang, Y.; Zhang, Y.; Xu, Y.; Ding, K. Identification of new small-molecule inducers of estrogen-related receptor α (ERRα) degradation. ACS Med. Chem. Lett., 2019, 10(5), 767-772.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00025] [PMID: 31097997]
[58]
Wang, L.; Guillen, V.S.; Sharma, N.; Flessa, K.; Min, J.; Carlson, K.E.; Toy, W.; Braqi, S.; Katzenellenbogen, B.S.; Katzenellenbogen, J.A.; Chandarlapaty, S.; Sharma, A.; Toy, W.; Braqi, S.; Katzenellenbogen, B.S.; Katzenellenbogen, J.A.; Chandarlapaty, S.; Sharma, A. New class of selective estrogen receptor degraders (SERDs): expanding the toolbox of PROTAC degrons. ACS Med. Chem. Lett., 2018, 9(8), 803-808.
[http://dx.doi.org/10.1021/acsmedchemlett.8b00106] [PMID: 30128071]
[59]
Li, Y.; Zhang, S.; Zhang, J.; Hu, Z.; Xiao, Y.; Huang, J.; Dong, C.; Huang, S.; Zhou, H.B. Exploring the PROTAC degron candidates: OBHSA with different side chains as novel selective estrogen receptor degraders (SERDs). Eur. J. Med. Chem., 2019, 172, 48-61.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.058] [PMID: 30939353]
[60]
Palmer, R.H.; Vernersson, E.; Grabbe, C.; Hallberg, B. Anaplastic lymphoma kinase: signalling in development and disease. Biochem. J., 2009, 420(3), 345-361.
[http://dx.doi.org/10.1042/BJ20090387] [PMID: 19459784]
[61]
Morris, S.W.; Kirstein, M.N.; Valentine, M.B.; Dittmer, K.G.; Shapiro, D.N.; Saltman, D.L.; Look, A.T. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science, 1994, 263(5151), 1281-1284.
[http://dx.doi.org/10.1126/science.8122112] [PMID: 8122112]
[62]
Powell, C.E.; Gao, Y.; Tan, L.; Donovan, K.A.; Nowak, R.P.; Loehr, A.; Bahcall, M.; Fischer, E.S.; Jänne, P.A.; George, R.E.; Gray, N.S. Chemically induced degradation of anaplastic lymphoma kinase (ALK). J. Med. Chem., 2018, 61(9), 4249-4255.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01655] [PMID: 29660984]
[63]
Zhang, C.; Han, X.R.; Yang, X.; Jiang, B.; Liu, J.; Xiong, Y.; Jin, J. Proteolysis targeting chimeras (PROTACs) of anaplastic lymphoma kinase (ALK). Eur. J. Med. Chem., 2018, 151, 304-314.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.071] [PMID: 29627725]
[64]
Kang, C.H.; Lee, D.H.; Lee, C.O.; Du Ha, J.; Park, C.H.; Hwang, J.Y. Induced protein degradation of anaplastic lymphoma kinase (ALK) by proteolysis targeting chimera (PROTAC). Biochem. Biophys. Res. Commun., 2018, 505(2), 542-547.
[http://dx.doi.org/10.1016/j.bbrc.2018.09.169] [PMID: 30274779]
[65]
Ren, R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat. Rev. Cancer, 2005, 5(3), 172-183.
[http://dx.doi.org/10.1038/nrc1567] [PMID: 15719031]
[66]
Lai, A.C.; Toure, M.; Hellerschmied, D.; Salami, J.; Jaime-Figueroa, S.; Ko, E.; Hines, D.J.; Crews, C.M. Modular PROTAC design for the degradation of oncogenic BCR-ABL. Angew. Chem. Int. Ed. Engl., 2016, 55(2), 807-810.
[http://dx.doi.org/10.1002/anie.201507634] [PMID: 26593377]
[67]
Zhao, Q.; Ren, C.; Liu, L.; Chen, J.; Shao, Y.; Sun, N.; Sun, R.; Kong, Y.; Ding, X.; Zhang, X.; Xu, Y.; Yang, B.; Yin, Q.; Yang, X.; Jiang, B. Discovery of SIAIS178 as an effective BCR-ABL degrader by recruiting von hippel-lindau (VHL) E3 ubiquitin ligase. J. Med. Chem., 2019, 62(20), 9281-9298.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01264] [PMID: 31539241]
[68]
Demizu, Y.; Shibata, N.; Hattori, T.; Ohoka, N.; Motoi, H.; Misawa, T.; Shoda, T.; Naito, M.; Kurihara, M. Development of BCR-ABL degradation inducers via the conjugation of an imatinib derivative and a cIAP1 ligand. Bioorg. Med. Chem. Lett., 2016, 26(20), 4865-4869.
[http://dx.doi.org/10.1016/j.bmcl.2016.09.041] [PMID: 27666635]
[69]
Shimokawa, K.; Shibata, N.; Sameshima, T.; Miyamoto, N.; Ujikawa, O.; Nara, H.; Ohoka, N.; Hattori, T.; Cho, N.; Naito, M. Targeting the allosteric site of oncoprotein BCR-ABL as an alternative strategy for effective target protein degradation. ACS Med. Chem. Lett., 2017, 8(10), 1042-1047.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00247] [PMID: 29057048]
[70]
Shibata, N.; Shimokawa, K.; Nagai, K.; Ohoka, N.; Hattori, T.; Miyamoto, N.; Ujikawa, O.; Sameshima, T.; Nara, H.; Cho, N.; Naito, M. Pharmacological difference between degrader and inhibitor against oncogenic BCR-ABL kinase. Sci. Rep., 2018, 8(1), 13549.
[http://dx.doi.org/10.1038/s41598-018-31913-5] [PMID: 30202081]
[71]
Shibata, N.; Ohoka, N.; Hattori, T.; Naito, M. Development of a potent protein degrader against oncogenic BCR-ABL protein. Chem. Pharm. Bull. (Tokyo), 2019, 67(3), 165-172.
[http://dx.doi.org/10.1248/cpb.c18-00703] [PMID: 30827996]
[72]
Mohamed, A.J.; Yu, L.; Bäckesjö, C-M.; Vargas, L.; Faryal, R.; Aints, A.; Christensson, B.; Berglöf, A.; Vihinen, M.; Nore, B.F.; Smith, C.I. Bruton’s tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol. Rev., 2009, 228(1), 58-73.
[http://dx.doi.org/10.1111/j.1600-065X.2008.00741.x] [PMID: 19290921]
[73]
Crofford, L.J.; Nyhoff, L.E.; Sheehan, J.H.; Kendall, P.L. The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy. Expert Rev. Clin. Immunol., 2016, 12(7), 763-773.
[http://dx.doi.org/10.1586/1744666X.2016.1152888] [PMID: 26864273]
[74]
Woyach, J.A.; Furman, R.R.; Liu, T.M.; Ozer, H.G.; Zapatka, M.; Ruppert, A.S.; Xue, L.; Li, D.H.; Steggerda, S.M.; Versele, M.; Dave, S.S.; Zhang, J.; Yilmaz, A.S.; Jaglowski, S.M.; Blum, K.A.; Lozanski, A.; Lozanski, G.; James, D.F.; Barrientos, J.C.; Lichter, P.; Stilgenbauer, S.; Buggy, J.J.; Chang, B.Y.; Johnson, A.J.; Byrd, J.C. Resistance mechanisms for the Bruton’s tyrosine kinase inhibitor ibrutinib. N. Engl. J. Med., 2014, 370(24), 2286-2294.
[http://dx.doi.org/10.1056/NEJMoa1400029] [PMID: 24869598]
[75]
Sun, Y.; Zhao, X.; Ding, N.; Gao, H.; Wu, Y.; Yang, Y.; Zhao, M.; Hwang, J.; Song, Y.; Liu, W.; Rao, Y.; Song, Y. PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies. Cell Res., 2018, 28(7), 779-781.
[http://dx.doi.org/10.1038/s41422-018-0055-1] [PMID: 29875397]
[76]
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. Targeting the C481S ibrutinib-resistance mutation in Bruton’s tyrosine kinase using PROTAC-mediated degradation. Biochemistry, 2018, 57(26), 3564-3575.
[http://dx.doi.org/10.1021/acs.biochem.8b00391] [PMID: 29851337]
[77]
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.; Shi, K.; Choi, H.G.; Griffin, J.D.; Li, Y.; Treon, S.P.; Fischer, E.S.; Bradner, J.E.; Tan, L.; Gray, N.S. A chemoproteomic approach to query the degradable kinome using a multi-kinase degrader. Cell Chem. Biol., 2018, 25(1), 88.e6-99.e6.
[http://dx.doi.org/10.1016/j.chembiol.2017.10.005] [PMID: 29129717]
[78]
Zorba, A.; Nguyen, C.; Xu, Y.; Starr, J.; Borzilleri, K.; Smith, J.; Zhu, H.; Farley, K.A.; Ding, W.; Schiemer, J.; Feng, X.; Chang, J.S.; Uccello, D.P.; Young, J.A.; Garcia-Irrizary, C.N.; Czabaniuk, L.; Schuff, B.; Oliver, R.; Montgomery, J.; Hayward, M.M.; Coe, J.; Chen, J.; Niosi, M.; Luthra, S.; Shah, J.C.; El-Kattan, A.; Qiu, X.; West, G.M.; Noe, M.C.; Shanmugasundaram, V.; Gilbert, A.M.; Brown, M.F.; Calabrese, M.F. Delineating the role of cooperativity in the design of potent PROTACs for BTK. Proc. Natl. Acad. Sci. USA, 2018, 115(31), E7285-E7292.
[http://dx.doi.org/10.1073/pnas.1803662115] [PMID: 30012605]
[79]
Krajcovicova, S.; Jorda, R.; Hendrychova, D.; Krystof, V.; Soural, M. Solid-phase synthesis for thalidomide-based proteolysis-targeting chimeras (PROTAC). Chem. Commun. (Camb.), 2019, 55(7), 929-932.
[http://dx.doi.org/10.1039/C8CC08716D] [PMID: 30601480]
[80]
Sun, Y.; Ding, N.; Song, Y.; Yang, Z.; Liu, W.; Zhu, J.; Rao, Y. Degradation of Bruton’s tyrosine kinase mutants by PROTACs for potential treatment of ibrutinib-resistant non-Hodgkin lymphomas. Leukemia, 2019, 33(8), 2105-2110.
[http://dx.doi.org/10.1038/s41375-019-0440-x] [PMID: 30858551]
[81]
Wu, M.; Li, C.; Zhu, X. FLT3 inhibitors in acute myeloid leukemia. J. Hematol. Oncol., 2018, 11(1), 133-145.
[http://dx.doi.org/10.1186/s13045-018-0675-4] [PMID: 30514344]
[82]
Smith, C.C.; Wang, Q.; Chin, C.S.; Salerno, S.; Damon, L.E.; Levis, M.J.; Perl, A.E.; Travers, K.J.; Wang, S.; Hunt, J.P.; Zarrinkar, P.P.; Schadt, E.E.; Kasarskis, A.; Kuriyan, J.; Shah, N.P. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature, 2012, 485(7397), 260-263.
[http://dx.doi.org/10.1038/nature11016] [PMID: 22504184]
[83]
Peng, J.; Marshall, N.F.; Price, D.H. Identification of a cyclin subunit required for the function of Drosophila P-TEFb. J. Biol. Chem., 1998, 273(22), 13855-13860.
[http://dx.doi.org/10.1074/jbc.273.22.13855] [PMID: 9593731]
[84]
Byrd, J.C.; Lin, T.S.; Dalton, J.T.; Wu, D.; Phelps, M.A.; Fischer, B.; Moran, M.; Blum, K.A.; Rovin, B.; Brooker-McEldowney, M.; Broering, S.; Schaaf, L.J.; Johnson, A.J.; Lucas, D.M.; Heerema, N.A.; Lozanski, G.; Young, D.C.; Suarez, J.R.; Colevas, A.D.; Grever, M.R. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood, 2007, 109(2), 399-404.
[http://dx.doi.org/10.1182/blood-2006-05-020735] [PMID: 17003373]
[85]
Robb, C.M.; Contreras, J.I.; Kour, S.; Taylor, M.A.; Abid, M.; Sonawane, Y.A.; Zahid, M.; Murry, D.J.; Natarajan, A.; Rana, S. Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC). Chem. Commun. (Camb.), 2017, 53(54), 7577-7580.
[http://dx.doi.org/10.1039/C7CC03879H] [PMID: 28636052]
[86]
Olson, C.M.; Jiang, B.; Erb, M.A.; Liang, Y.; Doctor, Z.M.; Zhang, Z.; Zhang, T.; Kwiatkowski, N.; Boukhali, M.; Green, J.L.; Haas, W.; Nomanbhoy, T.; Fischer, E.S.; Young, R.A.; Bradner, J.E.; Winter, G.E.; Gray, N.S. Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation. Nat. Chem. Biol., 2018, 14(2), 163-170.
[http://dx.doi.org/10.1038/nchembio.2538] [PMID: 29251720]
[87]
Bian, J.; Ren, J.; Li, Y.; Wang, J.; Xu, X.; Feng, Y.; Tang, H.; Wang, Y.; Li, Z. Discovery of wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity. Bioorg. Chem., 2018, 81, 373-381.
[http://dx.doi.org/10.1016/j.bioorg.2018.08.028] [PMID: 30196207]
[88]
Humphries, F.; Yang, S.; Wang, B.; Moynagh, P.N. RIP kinases: key decision makers in cell death and innate immunity. Cell Death Differ., 2015, 22(2), 225-236.
[http://dx.doi.org/10.1038/cdd.2014.126] [PMID: 25146926]
[89]
Lee, B.Y.; Timpson, P.; Horvath, L.G.; Daly, R.J. FAK signaling in human cancer as a target for therapeutics. Pharmacol. Ther., 2015, 146, 132-149.
[http://dx.doi.org/10.1016/j.pharmthera.2014.10.001] [PMID: 25316657]
[90]
Sulzmaier, F.J.; Jean, C.; Schlaepfer, D.D. FAK in cancer: mechanistic findings and clinical applications. Nat. Rev. Cancer, 2014, 14(9), 598-610.
[http://dx.doi.org/10.1038/nrc3792] [PMID: 25098269]
[91]
Cromm, P.M.; Samarasinghe, K.T.G.; Hines, J.; Crews, C.M. Addressing kinase-independent functions of FAK via PROTAC-mediated degradation. J. Am. Chem. Soc., 2018, 140(49), 17019-17026.
[http://dx.doi.org/10.1021/jacs.8b08008] [PMID: 30444612]
[92]
Popow, J.; Arnhof, H.; Bader, G.; Berger, H.; Ciulli, A.; Covini, D.; Dank, C.; Gmaschitz, T.; Greb, P.; Karolyi-Özguer, J.; Koegl, M.; McConnell, D.B.; Pearson, M.; Rieger, M.; Rinnenthal, J.; Roessler, V.; Schrenk, A.; Spina, M.; Steurer, S.; Trainor, N.; Traxler, E.; Wieshofer, C.; Zoephel, A.; Ettmayer, P. Highly selective PTK2 proteolysis targeting chimeras to probe focal adhesion kinase scaffolding functions. J. Med. Chem., 2019, 62(5), 2508-2520.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01826] [PMID: 30739444]
[93]
Gao, H.; Wu, Y.; Sun, Y.; Yang, Y.; Zhou, G.; Rao, Y. Design, synthesis, and evaluation of highly potent FAK-targeting PROTACs. ACS Med. Chem. Lett., 2019, 11(10), 1855-1862.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00372]] [PMID: 33062164]
[94]
Yu, T.; Yang, Y.; Yin, D.Q.; Hong, S.; Son, Y.J.; Kim, J.H.; Cho, J.Y. TBK1 inhibitors: a review of patent literature (2011 - 2014). Expert Opin. Ther. Pat., 2015, 25(12), 1385-1396.
[http://dx.doi.org/10.1517/13543776.2015.1081168] [PMID: 26293650]
[95]
Clark, K.; Plater, L.; Peggie, M.; Cohen, P. Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J. Biol. Chem., 2009, 284(21), 14136-14146.
[http://dx.doi.org/10.1074/jbc.M109.000414] [PMID: 19307177]
[96]
Crew, A.P.; Raina, K.; Dong, H.; Qian, Y.; Wang, J.; Vigil, D.; Serebrenik, Y.V.; Hamman, B.D.; Morgan, A.; Ferraro, C.; Siu, K.; Neklesa, T.K.; Winkler, J.D.; Coleman, K.G.; Crews, C.M. Identification and characterization of von hippel lindau-recruiting proteolysis targeting chimeras (PROTACs) of TANK-binding kinase 1. J. Med. Chem., 2018, 61(2), 583-598.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00635] [PMID: 28692295]
[97]
Gallenkamp, D.; Gelato, K.A.; Haendler, B.; Weinmann, H. Bromodomains and their pharmacological inhibitors. ChemMedChem, 2014, 9(3), 438-464.
[http://dx.doi.org/10.1002/cmdc.201300434] [PMID: 24497428]
[98]
Belkina, A.C.; Denis, G.V. BET domain co-regulators in obesity, inflammation and cancer. Nat. Rev. Cancer, 2012, 12(7), 465-477.
[http://dx.doi.org/10.1038/nrc3256] [PMID: 22722403]
[99]
Baratta, M.G.; Schinzel, A.C.; Zwang, Y.; Bandopadhayay, P.; Bowman-Colin, C.; Kutt, J.; Curtis, J.; Piao, H.; Wong, L.C.; Kung, A.L.; Beroukhim, R.; Bradner, J.E.; Drapkin, R.; Hahn, W.C.; Liu, J.F.; Livingston, D.M. An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma. Proc. Natl. Acad. Sci. USA, 2015, 112(1), 232-237.
[http://dx.doi.org/10.1073/pnas.1422165112] [PMID: 25535366]
[100]
Zuber, J.; Shi, J.; Wang, E.; Rappaport, A.R.; Herrmann, H.; Sison, E.A.; Magoon, D.; Qi, J.; Blatt, K.; Wunderlich, M.; Taylor, M.J.; Johns, C.; Chicas, A.; Mulloy, J.C.; Kogan, S.C.; Brown, P.; Valent, P.; Bradner, J.E.; Lowe, S.W.; Vakoc, C.R. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature, 2011, 478(7370), 524-528.
[http://dx.doi.org/10.1038/nature10334] [PMID: 21814200]
[101]
Zengerle, M.; Chan, K.H.; Ciulli, A. Selective small molecule induced degradation of the BET bromodomain protein BRD4. ACS Chem. Biol., 2015, 10(8), 1770-1777.
[http://dx.doi.org/10.1021/acschembio.5b00216] [PMID: 26035625]
[102]
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. Hijacking the E3 ubiquitin ligase cereblon to efficiently target BRD4. Chem. Biol., 2015, 22(6), 755-763.
[http://dx.doi.org/10.1016/j.chembiol.2015.05.009] [PMID: 26051217]
[103]
Winter, G.E.; Buckley, D.L.; Paulk, J.; Roberts, J.M.; Souza, A.; Dhe-Paganon, S.; Bradner, J.E. Drug development. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science, 2015, 348(6241), 1376-1381.
[http://dx.doi.org/10.1126/science.aab1433] [PMID: 25999370]
[104]
Zhou, B.; Hu, J.; Xu, F.; Chen, Z.; Bai, L.; Fernandez-Salas, E.; Lin, M.; Liu, L.; Yang, C.Y.; Zhao, Y.; McEachern, D.; Przybranowski, S.; Wen, B.; Sun, D.; Wang, S. Discovery of a small-molecule degrader of bromodomain and extra-terminal (BET) proteins with picomolar cellular potencies and capable of achieving tumor regression. J. Med. Chem., 2018, 61(2), 462-481.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01816] [PMID: 28339196]
[105]
Qin, C.; Hu, Y.; Zhou, B.; Fernandez-Salas, E.; Yang, C.Y.; Liu, L.; McEachern, D.; Przybranowski, S.; Wang, M.; Stuckey, J.; Meagher, J.; Bai, L.; Chen, Z.; Lin, M.; Yang, J.; Ziazadeh, D.N.; Xu, F.; Hu, J.; Xiang, W.; Huang, L.; Li, S.; Wen, B.; Sun, D.; Wang, S. Discovery of QCA570 as an exceptionally potent and efficacious proteolysis targeting chimera (PROTAC) degrader of the bromodomain and extra-terminal (BET) proteins capable of inducing complete and durable tumor regression. J. Med. Chem., 2018, 61(15), 6685-6704.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00506] [PMID: 30019901]
[106]
Wang, S.; Song, Y.; Wang, Y.; Gao, Y.; Yu, S.; Zhao, Q.; Jin, X.; Lu, H. Design and synthesis of novel bispecific molecules for inducing BRD4 protein degradation. Chem. Res. Chin. Univ., 2018, 34(1), 67-74.
[http://dx.doi.org/10.1007/s40242-018-7272-5]
[107]
Bai, L.; Zhou, B.; Yang, C-Y.; Ji, J.; McEachern, D.; Przybranowski, S.; Jiang, H.; Hu, J.; Xu, F.; Zhao, Y.; Liu, L.; Fernandez-Salas, E.; Xu, J.; Dou, Y.; Wen, B.; Sun, D.; Meagher, J.; Stuckey, J.; Hayes, D.F.; Li, S.; Ellis, M.J.; Wang, S. Targeted degradation of BET proteins in triple-negative breast cancer. Cancer Res., 2017, 77(9), 2476-2487.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-2622] [PMID: 28209615]
[108]
Gadd, M.S.; Testa, A.; Lucas, X.; Chan, K.H.; Chen, W.; Lamont, D.J.; Zengerle, M.; Ciulli, A. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat. Chem. Biol., 2017, 13(5), 514-521.
[http://dx.doi.org/10.1038/nchembio.2329] [PMID: 28288108]
[109]
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.; Zhang, T.; Mancias, J.D.; Gray, N.S.; Bradner, J.E.; Fischer, E.S. Plasticity in binding confers selectivity in ligand-induced protein degradation. Nat. Chem. Biol., 2018, 14(7), 706-714.
[http://dx.doi.org/10.1038/s41589-018-0055-y] [PMID: 29892083]
[110]
Zhang, F.; Wu, Z.; Chen, P.; Zhang, J.; Wang, T.; Zhou, J.; Zhang, H. Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide. Bioorg. Med. Chem., 2020, 28(1)115228
[http://dx.doi.org/10.1016/j.bmc.2019.115228] [PMID: 31813613]
[111]
Donovan, M.; Olofsson, B.; Gustafson, A.L.; Dencker, L.; Eriksson, U. The cellular retinoic acid binding proteins. J. Steroid Biochem. Mol. Biol., 1995, 53(1-6), 459-465.
[http://dx.doi.org/10.1016/0960-0760(95)00092-E] [PMID: 7626495]
[112]
Uhrig, M.; Brechlin, P.; Jahn, O.; Knyazev, Y.; Weninger, A.; Busia, L.; Honarnejad, K.; Otto, M.; Hartmann, T. Upregulation of CRABP1 in human neuroblastoma cells overproducing the Alzheimer-typical Abeta42 reduces their differentiation potential. BMC Med., 2008, 6, 38-49.
[http://dx.doi.org/10.1186/1741-7015-6-38] [PMID: 19087254]
[113]
Vo, H.P.; Crowe, D.L. Transcriptional regulation of retinoic acid responsive genes by cellular retinoic acid binding protein-II modulates RA mediated tumor cell proliferation and invasion. Anticancer Res., 1998, 18(1A), 217-224.
[PMID: 9568080]
[114]
Itoh, Y.; Ishikawa, M.; Naito, M.; Hashimoto, Y. Protein knockdown using methyl bestatin-ligand hybrid molecules: design and synthesis of inducers of ubiquitination-mediated degradation of cellular retinoic acid-binding proteins. J. Am. Chem. Soc., 2010, 132(16), 5820-5826.
[http://dx.doi.org/10.1021/ja100691p] [PMID: 20369832]
[115]
Itoh, Y.; Ishikawa, M.; Kitaguchi, R.; Sato, S.; Naito, M.; Hashimoto, Y. Development of target protein-selective degradation inducer for protein knockdown. Bioorg. Med. Chem., 2011, 19(10), 3229-3241.
[http://dx.doi.org/10.1016/j.bmc.2011.03.057] [PMID: 21515062]
[116]
Itoh, Y.; Ishikawa, M.; Kitaguchi, R.; Okuhira, K.; Naito, M.; Hashimoto, Y. Double protein knockdown of cIAP1 and CRABP-II using a hybrid molecule consisting of ATRA and IAPs antagonist. Bioorg. Med. Chem. Lett., 2012, 22(13), 4453-4457.
[http://dx.doi.org/10.1016/j.bmcl.2012.04.134] [PMID: 22658364]
[117]
Le Douarin, B.; Nielsen, A.L.; Garnier, J.M.; Ichinose, H.; Jeanmougin, F.; Losson, R.; Chambon, P. A possible involvement of TIF1 α and TIF1 β in the epigenetic control of transcription by nuclear receptors. EMBO J., 1996, 15(23), 6701-6715.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb01060.x] [PMID: 8978696]
[118]
Khetchoumian, K.; Teletin, M.; Tisserand, J.; Mark, M.; Herquel, B.; Ignat, M.; Zucman-Rossi, J.; Cammas, F.; Lerouge, T.; Thibault, C.; Metzger, D.; Chambon, P.; Losson, R. Loss of Trim24 (Tif1alpha) gene function confers oncogenic activity to retinoic acid receptor alpha. Nat. Genet., 2007, 39(12), 1500-1506.
[http://dx.doi.org/10.1038/ng.2007.15] [PMID: 18026104]
[119]
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.; Seo, H.S.; Dhe-Paganon, S.; Kwiatkowski, N.P.; Perry, J.A.; Qi, J.; Gray, N.S.; Bradner, J.E. Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands. Nat. Chem. Biol., 2018, 14(4), 405-412.
[http://dx.doi.org/10.1038/s41589-018-0010-y] [PMID: 29507391]
[120]
Levy, D.E.; Darnell, J.E. Jr. Stats: transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol., 2002, 3(9), 651-662.
[http://dx.doi.org/10.1038/nrm909] [PMID: 12209125]
[121]
Huang, Q.; Zhong, Y.; Dong, H.; Zheng, Q.; Shi, S.; Zhu, K.; Qu, X.; Hu, W.; Zhang, X.; Wang, Y. Revisiting signal transducer and activator of transcription 3 (STAT3) as an anticancer target and its inhibitor discovery: where are we and where should we go? Eur. J. Med. Chem., 2020, 187111922
[http://dx.doi.org/10.1016/j.ejmech.2019.111922] [PMID: 31810784]
[122]
Bai, L.; Zhou, H.; Xu, R.; Zhao, Y.; Chinnaswamy, K.; McEachern, D.; Chen, J.; Yang, C.Y.; Liu, Z.; Wang, M.; Liu, L.; Jiang, H.; Wen, B.; Kumar, P.; Meagher, J.L.; Sun, D.; Stuckey, J.A.; Wang, S. A potent and selective small-molecule degrader of STAT3 achieves complete tumor regression in vivo. Cancer Cell, 2019, 36(5), 498.e17-511.e17.
[http://dx.doi.org/10.1016/j.ccell.2019.10.002] [PMID: 31715132]
[123]
Burslem, G.M.; Crews, C.M. Small-molecule modulation of protein homeostasis. Chem. Rev., 2017, 117(17), 11269-11301.
[http://dx.doi.org/10.1021/acs.chemrev.7b00077] [PMID: 28777566]
[124]
Hwang, D.J.; He, Y.; Ponnusamy, S.; Mohler, M.L.; Thiyagarajan, T.; McEwan, I.J.; Narayanan, R.; Miller, D.D. New generation of selective androgen receptor degraders: our initial design, synthesis, and biological evaluation of new compounds with enzalutamide-resistant prostate cancer activity. J. Med. Chem., 2019, 62(2), 491-511.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00973] [PMID: 30525603]

Rights & Permissions Print Cite
Article Metrics
187
1
World Chagas Disease
© 2024 Bentham Science Publishers | Privacy Policy