Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

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

Review Article

Recent Developments in Medicinal Chemistry and Therapeutic Potential of Anti-Cancer PROTACs-Based Molecules

Author(s): Muhammad Zafar Irshad Khan, Adila Nazli, You-Lu Pan and Jian-Zhong Chen*

Volume 30, Issue 14, 2023

Published on: 04 November, 2022

Page: [1576 - 1622] Pages: 47

DOI: 10.2174/0929867329666220803112409

Price: $65

conference banner
Abstract

Background: PROTACs is an emerging technique that addresses the disease causing proteins by targeting protein degradation. PROTACs molecules are bifunctional small molecules that simultaneously bind to the protein of interest (POIs) and an E3 ligase followed by ubiquitination and degradation of the protein of interest by the proteasome.

Objective: PROTACs technology offers many advantages over classical inhibition such as PROTACs molecules can target intracellular proteins regardless of their function and have good tissue distribution. They are capable to target mutated and overexpressed proteins, thus potent molecules with the high degradation selectivity can be designed. Moreover, PROTACs molecules can target the undruggable proteome which makes up almost 85% of human proteins. Several PROTACs-based compounds have exhibited high therapeutic potency and some of them are currently under clinical trials.

Methods: Current article gives a comprehensive overview of the current development of PROTACs-based anticancer compounds along with the structure-activity relationship of the reported molecules.

Results: The development of PROTACs-based compounds and related research regarding medicinal chemistry is one of the most active and hot topics for research.

Conclusion: It is believed that the current review article can be helpful to understand the logical design of more efficacious PROTACs-based molecules with less toxicity and more selectivity.

Keywords: Targeted protein degradation, PROTACs, ubiquitination, degradation, structure activity relationship, medicinal chemistry.

[1]
Ottis, P.; Crews, C.M. Proteolysis-targeting chimeras: Induced protein degradation as a therapeutic strategy. ACS Chem. Biol., 2017, 12(4), 892-898.
[http://dx.doi.org/10.1021/acschembio.6b01068] [PMID: 28263557]
[2]
Cromm, P.M.; Crews, C.M. The proteasome in modern drug discovery: Second life of a highly valuable drug target. ACS Cent. Sci., 2017, 3(8), 830-838.
[http://dx.doi.org/10.1021/acscentsci.7b00252] [PMID: 28852696]
[3]
Xi, M.; Chen, Y.; Yang, H.; Xu, H.; Du, K.; Wu, C.; Xu, Y.; Deng, L.; Luo, X.; Yu, L.; Wu, Y.; Gao, X.; Cai, T.; Chen, B.; Shen, R.; Sun, H. Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation. Eur. J. Med. Chem., 2019, 174, 159-180.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.036] [PMID: 31035238]
[4]
Coux, O.; Tanaka, K.; Goldberg, A.L. Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem., 1996, 65(1), 801-847.
[http://dx.doi.org/10.1146/annurev.bi.65.070196.004101] [PMID: 8811196]
[5]
Bhattacharyya, S.; Yu, H.; Mim, C.; Matouschek, A. Regulated protein turnover: Snapshots of the proteasome in action. Nat. Rev. Mol. Cell Biol., 2014, 15(2), 122-133.
[http://dx.doi.org/10.1038/nrm3741] [PMID: 24452470]
[6]
Ebner, P.; Versteeg, G.A.; Ikeda, F. Ubiquitin enzymes in the regulation of immune responses. Crit. Rev. Biochem. Mol. Biol., 2017, 52(4), 425-460.
[http://dx.doi.org/10.1080/10409238.2017.1325829] [PMID: 28524749]
[7]
Tramutola, A. It is all about (U) biquitin: Role of altered ubiquitin-proteasome system and UCHL1 in Alzheimer disease. Oxid. Med. Cell. Longev., 2016, 2016, 2756068.
[8]
Finley, D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu. Rev. Biochem., 2009, 78, 477-513.
[http://dx.doi.org/10.1146/annurev.biochem.78.081507.101607] [PMID: 19489727]
[9]
Sun, X.; Rao, Y. PROTACs as potential therapeutic agents for cancer drug resistance. Biochemistry, 2020, 59(3), 240-249.
[http://dx.doi.org/10.1021/acs.biochem.9b00848] [PMID: 31661257]
[10]
Zhou, Y.; Xiao, Y. Chemoproteomic-driven discovery of covalent PROTACs; ACS Publications: USA, 2020.
[http://dx.doi.org/10.1021/acs.biochem.9b00795]
[11]
Fedorov, Y.; Anderson, E.M.; Birmingham, A.; Reynolds, A.; Karpilow, J.; Robinson, K.; Leake, D.; Marshall, W.S.; Khvorova, A. Off-target effects by siRNA can induce toxic phenotype. RNA, 2006, 12(7), 1188-1196.
[http://dx.doi.org/10.1261/rna.28106] [PMID: 16682561]
[12]
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]
[13]
Tinworth, C.P.; Lithgow, H.; Churcher, I. Small molecule-mediated protein knockdown as a new approach to drug discovery. MedChemComm, 2016, 7(12), 2206-2216.
[http://dx.doi.org/10.1039/C6MD00347H]
[14]
Montrose, K.; Krissansen, G.W. Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus. Biochem. Biophys. Res. Commun., 2014, 453(4), 735-740.
[http://dx.doi.org/10.1016/j.bbrc.2014.10.006] [PMID: 25305486]
[15]
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]
[16]
Yang, C-Y.; Qin, C.; Bai, L.; Wang, S. Small-molecule PROTAC degraders of the Bromodomain and Extra Terminal (BET) proteins - A review. Drug Discov. Today. Technol., 2019, 31, 43-51.
[http://dx.doi.org/10.1016/j.ddtec.2019.04.001] [PMID: 31200858]
[17]
Flanagan, J.J.; Neklesa, T.K. Targeting nuclear receptors with PROTACS degraders. Mol. Cell. Endocrinol., 2019, 493, 110452.
[http://dx.doi.org/10.1016/j.mce.2019.110452] [PMID: 31125586]
[18]
Long, M.J.; Poganik, J.R.; Aye, Y. On-demand targeting: Investigating biology with proximity-directed chemistry. J. Am. Chem. Soc., 2016, 138(11), 3610-3622.
[http://dx.doi.org/10.1021/jacs.5b12608] [PMID: 26907082]
[19]
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]
[20]
Cromm, P.M.; Crews, C.M. Targeted protein degradation: From chemical biology to drug discovery. Cell Chem. Biol., 2017, 24(9), 1181-1190.
[http://dx.doi.org/10.1016/j.chembiol.2017.05.024] [PMID: 28648379]
[21]
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]
[22]
Kargbo, R.B. PROTACS molecules for the treatment of autoimmune disorders; ACS Publications: USA, 2019.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00042]
[23]
Kargbo, R.B. PROTACS Degradation of IRAK4 for the Treatment of Neurodegenerative and Cardiovascular Diseases; ACS Publications: USA, 2019.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00385]
[24]
De, Wispelaere W.; Du, G.; Donovan, K.A.; Zhang, T.; Eleuteri, N.A.; Yuan, J.C. Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations. Nat. Commun., 2019, 10(1), 1-11.
[PMID: 30602773]
[25]
Kargbo, R.B. Treatment of Alzheimer’s by PROTACS-Tau protein degradation; ACS Publications: USA, 2019.
[26]
Kargbo, R.B. Treatment of prostate cancers and Kennedy’s disease by PROTACS-androgen receptor degradation; ACS Publications: USA, 2019.
[27]
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), 78-87.e5.
[http://dx.doi.org/10.1016/j.chembiol.2017.09.010] [PMID: 29129718]
[28]
Pettersson, M.; Crews, C.M. PROteolysis TArgeting Chimeras (PROTACs) - past, present and future. Drug Discov. Today. Technol., 2019, 31(31), 15-27.
[http://dx.doi.org/10.1016/j.ddtec.2019.01.002] [PMID: 31200855]
[29]
Khan, M.Z.I.; Zahra, S.S.; Ahmed, M.; Fatima, H.; Mirza, B.; Haq, I.U.; Khan, S.U. Polyphenolic profiling of Ipomoea carnea Jacq. by HPLC-DAD and its implications in oxidative stress and cancer. Nat. Prod. Res., 2019, 33(14), 2099-2104.
[http://dx.doi.org/10.1080/14786419.2018.1482551] [PMID: 29873254]
[30]
Keri, R.S.; Patil, M.R.; Patil, S.A.; Budagumpi, S. A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry. Eur. J. Med. Chem., 2015, 89, 207-251.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.059] [PMID: 25462241]
[31]
Churcher, I. PROTACs-induced protein degradation in drug discovery: Breaking the rules or just making new ones? J. Med. Chem., 2018, 61(2), 444-452.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01272] [PMID: 29144739]
[32]
Liu, J.; Ma, J.; Liu, Y.; Xia, J.; Li, Y.; Wang, Z.P.; Wei, W. PROTACs: A novel strategy for cancer therapy. Semin. Cancer Biol., 2020, 67(Pt 2), 171-179.
[http://dx.doi.org/10.1016/j.semcancer.2020.02.006] [PMID: 32058059]
[33]
Sakamoto, K.M. Protacs for treatment of cancer. Pediatr. Res., 2010, 67(5), 505-508.
[http://dx.doi.org/10.1203/PDR.0b013e3181d35017] [PMID: 20075761]
[34]
Buschbeck, M. Strategies to overcome resistance to targeted protein kinase inhibitors in the treatment of cancer. Drugs R D., 2006, 7(2), 73-86.
[http://dx.doi.org/10.2165/00126839-200607020-00002] [PMID: 16542054]
[35]
Özvegy-Laczka, C.; Cserepes, J.; Elkind, N.B.; Sarkadi, B. Tyrosine kinase inhibitor resistance in cancer: Role of ABC multidrug transporters. Drug Resist. Updat., 2005, 8(1-2), 15-26.
[http://dx.doi.org/10.1016/j.drup.2005.02.002] [PMID: 15939339]
[36]
Camidge, D.R.; Pao, W.; Sequist, L.V. Acquired resistance to TKIs in solid tumours: Learning from lung cancer. Nat. Rev. Clin. Oncol., 2014, 11(8), 473-481.
[http://dx.doi.org/10.1038/nrclinonc.2014.104] [PMID: 24981256]
[37]
Pepermans, R.A. Prossnitz, E.R. ERα-targeted endocrine therapy, resistance and the role of GPER. Steroids, 2019, 152, 108493.
[http://dx.doi.org/10.1016/j.steroids.2019.108493] [PMID: 31518595]
[38]
Russo, J.; Russo, I.H. The role of estrogen in the initiation of breast cancer. J. Steroid Biochem. Mol. Biol., 2006, 102(1-5), 89-96.
[http://dx.doi.org/10.1016/j.jsbmb.2006.09.004] [PMID: 17113977]
[39]
Ariazi, E.A.; Ariazi, J.L.; Cordera, F.; Jordan, V.C. Estrogen receptors as therapeutic targets in breast cancer. Curr. Top. Med. Chem., 2006, 6(3), 181-202.
[http://dx.doi.org/10.2174/156802606776173483] [PMID: 16515478]
[40]
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]
[41]
Flanagan, J.; Qian, Y.; Gough, S.; Andreoli, M.; Bookbinder, M.; Cadelina, G. Abstract P5-04-18: ARV-471, an oral estrogen receptor PROTACS degrader for breast cancer. Cancer Res., 2019, 79(4_Suppl.), P5-04-18.
[42]
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 (PROTACS) degrader of estrogen receptor (ER). J. Med. Chem., 2019, 62(3), 1420-1442.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01572] [PMID: 30990042]
[43]
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. New class of selective estrogen receptor degraders (SERDs): Expanding the toolbox of PROTACS degrons. ACS Med. Chem. Lett., 2018, 9(8), 803-808.
[http://dx.doi.org/10.1021/acsmedchemlett.8b00106] [PMID: 30128071]
[44]
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 α. ACS Chem. Biol., 2018, 13(3), 628-635.
[http://dx.doi.org/10.1021/acschembio.7b00985] [PMID: 29271628]
[45]
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]
[46]
Dai, Y.; Yue, N.; Gong, J.; Liu, C.; Li, Q.; Zhou, J.; Huang, W.; Qian, H. Development of cell-permeable peptide-based PROTACs targeting estrogen receptor α. Eur. J. Med. Chem., 2020, 187, 111967.
[http://dx.doi.org/10.1016/j.ejmech.2019.111967] [PMID: 31865016]
[47]
Gonzalez, T.L.; Hancock, M.; Sun, S.; Gersch, C.L.; Larios, J.M.; David, W.; Hu, J.; Hayes, D.F.; Wang, S.; Rae, J.M. Targeted degradation of activating estrogen receptor α ligand-binding domain mutations in human breast cancer. Breast Cancer Res. Treat., 2020, 180(3), 611-622.
[http://dx.doi.org/10.1007/s10549-020-05564-y] [PMID: 32067153]
[48]
Singh, S.P.; Dammeijer, F.; Hendriks, R.W. Role of Bruton’s tyrosine kinase in B cells and malignancies. Mol. Cancer, 2018, 17(1), 1-23.
[PMID: 29304823]
[49]
Campbell, R.; Chong, G.; Hawkes, E.A. Novel indications for Bruton’s tyrosine kinase inhibitors, beyond hematological malignancies. J. Clin. Med., 2018, 7(4), 62.
[http://dx.doi.org/10.3390/jcm7040062] [PMID: 29561760]
[50]
Liu, S.; Da, Y.; Wang, F.; Yan, R.; Shu, Y.; Lin, P. Targeted selective degradation of Bruton’s tyrosine kinase by PROTACs. Med. Chem. Res., 2020, 29(4), 802-808.
[http://dx.doi.org/10.1007/s00044-020-02526-3]
[51]
Zhu, S.; Jung, J.; Victor, E.; Arceo, J.; Gokhale, S.; Xie, P. Clinical trials of the BTK inhibitors Ibrutinib and Acalabrutinib in human diseases beyond B cell malignancies. Front. Oncol., 2021, 11, 737943.
[http://dx.doi.org/10.3389/fonc.2021.737943] [PMID: 34778053]
[52]
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]
[53]
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 PROTACS-mediated degradation. Biochemistry, 2018, 57(26), 3564-3575.
[http://dx.doi.org/10.1021/acs.biochem.8b00391] [PMID: 29851337]
[54]
Jaime-Figueroa, S.; Buhimschi, A.D.; Toure, M.; Hines, J.; Crews, C.M. Design, synthesis and biological evaluation of Proteolysis Targeting Chimeras (PROTACs) as a BTK degraders with improved pharmacokinetic properties. Bioorg. Med. Chem. Lett., 2020, 30(3), 126877.
[http://dx.doi.org/10.1016/j.bmcl.2019.126877] [PMID: 31879210]
[55]
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]
[56]
Dobrovolsky, D.; Wang, E.S.; Morrow, S.; Leahy, C.; Faust, T.; Nowak, R.P.; Donovan, K.A.; Yang, G.; Li, Z.; Fischer, E.S.; Treon, S.P.; Weinstock, D.M.; Gray, N.S. Bruton tyrosine kinase degradation as a therapeutic strategy for cancer. Blood, 2019, 133(9), 952-961.
[http://dx.doi.org/10.1182/blood-2018-07-862953] [PMID: 30545835]
[57]
Sundén, H.; Holland, M.C.; Poutiainen, P.K.; Jääskeläinen, T.; Pulkkinen, J.T.; Palvimo, J.J.; Olsson, R. Synthesis and biological evaluation of second-generation tropanol-based androgen receptor modulators. J. Med. Chem., 2015, 58(3), 1569-1574.
[http://dx.doi.org/10.1021/jm501995n] [PMID: 25646649]
[58]
Sanford, M. Enzalutamide: A review of its use in metastatic, castration-resistant prostate cancer. Drugs, 2013, 73(15), 1723-1732.
[http://dx.doi.org/10.1007/s40265-013-0129-9] [PMID: 24127223]
[59]
Watson, P.A.; Arora, V.K.; Sawyers, C.L. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat. Rev. Cancer, 2015, 15(12), 701-711.
[http://dx.doi.org/10.1038/nrc4016] [PMID: 26563462]
[60]
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]
[61]
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]
[62]
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]
[63]
Kregel, S.; Wang, C.; Han, X.; Xiao, L.; Fernandez-Salas, E.; Bawa, P.; McCollum, B.L.; Wilder-Romans, K.; Apel, I.J.; Cao, X.; Speers, C.; Wang, S.; Chinnaiyan, A.M. Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment. Neoplasia, 2020, 22(2), 111-119.
[http://dx.doi.org/10.1016/j.neo.2019.12.003] [PMID: 31931431]
[64]
Neklesa, T.; Snyder, L.; Willard, R.R.; Vitale, N.; Pizzano, J.; Gordon, D. ARV-110: An oral androgen receptor PROTACS degrader for prostate cancer. J. Clin. Oncol., 2019, 37, 259.
[http://dx.doi.org/10.1200/JCO.2019.37.7_suppl.259]
[65]
Jiang, F.; Wei, Q.; Li, H.; Li, H.; Cui, Y.; Ma, Y.; Chen, H.; Cao, P.; Lu, T.; Chen, Y. Discovery of novel small molecule induced selective degradation of the bromodomain and extra-terminal (BET) bromodomain protein BRD4 and BRD2 with cellular potencies. Bioorg. Med. Chem., 2020, 28(1), 115181.
[http://dx.doi.org/10.1016/j.bmc.2019.115181] [PMID: 31767403]
[66]
Filippakopoulos, P.; Picaud, S.; Mangos, M.; Keates, T.; Lambert, J.P.; Barsyte-Lovejoy, D.; Felletar, I.; Volkmer, R.; Müller, S.; Pawson, T.; Gingras, A.C.; Arrowsmith, C.H.; Knapp, S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell, 2012, 149(1), 214-231.
[http://dx.doi.org/10.1016/j.cell.2012.02.013] [PMID: 22464331]
[67]
Consortium, U. Reorganizing the protein space at the Universal Protein Resource (UniProt). Nucleic Acids Res., 2012, 40, D71-D75.
[http://dx.doi.org/10.1093/nar/gkr981] [PMID: 22102590]
[68]
Qin, C.; Hu, Y.; Zhou, B. Fernandez, Salas, E.; Yang, C.Y.; Liu, L. Discovery of QCA570 as an exceptionally potent and efficacious proteolysis targeting chimera (PROTACS) 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]
[69]
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]
[70]
Raina, K.; Lu, J.; Qian, Y.; Altieri, M.; Gordon, D.; Rossi, A.M.K.; 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]
[71]
Qiu, X.; Sun, N.; Kong, Y.; Li, Y.; Yang, X.; Jiang, B. Chemoselective synthesis of lenalidomide-based PRO-TACS library using alkylation reaction. Org. Lett., 2019, 21(10), 3838-3841.
[http://dx.doi.org/10.1021/acs.orglett.9b01326] [PMID: 31066567]
[72]
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]
[73]
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]
[74]
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]
[75]
Del, Mar, Noblejas-López, M.; Nieto, Jimenez, C.; Burgos, M.; Gómez, Juárez, M.; Montero, J.C.; Esparís, Ogando, A. Activity of BET-proteolysis targeting chimeric (PROTACS) compounds in triple negative breast cancer. J. Exp. Clin. Cancer Res., 2019, 38(1), 1-9.
[PMID: 30606223]
[76]
Shi, C.; Zhang, H.; Wang, P.; Wang, K.; Xu, D.; Wang, H.; Yin, L.; Zhang, S.; Zhang, Y. PROTAC induced-BET protein degradation exhibits potent anti-osteosarcoma activity by triggering apoptosis. Cell Death Dis., 2019, 10(11), 815.
[http://dx.doi.org/10.1038/s41419-019-2022-2] [PMID: 31653826]
[77]
Zoppi, V.; Hughes, S.J.; Maniaci, C.; Testa, A.; Gmaschitz, T.; Wieshofer, C.; Koegl, M.; Riching, K.M.; Daniels, D.L.; Spallarossa, A.; Ciulli, A. Wieshofer. Iterative design and optimization of initially inactive proteolysis targeting chimeras (PROTACs) identify VZ185 as a potent, fast, and selective von Hippel–Lindau (VHL) based dual degrader probe of BRD9 and BRD7. J. Med. Chem., 2019, 62(2), 699-726.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01413] [PMID: 30540463]
[78]
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]
[79]
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]
[80]
Druker, B.J. Perspectives on the development of imatinib and the future of cancer research. Nat. Med., 2009, 15(10), 1149-1152.
[http://dx.doi.org/10.1038/nm1009-1149] [PMID: 19812576]
[81]
Ichim, C.V. Kinase-independent mechanisms of resistance of leukemia stem cells to tyrosine kinase inhibitors. Stem Cells Transl. Med., 2014, 3(4), 405-415.
[http://dx.doi.org/10.5966/sctm.2012-0159] [PMID: 24598782]
[82]
Redaelli, S.; Mologni, L.; Rostagno, R.; Piazza, R.; Magistroni, V.; Ceccon, M.; Viltadi, M.; Flynn, D.; Gambacorti-Passerini, C. Three novel patient-derived BCR/ABL mutants show different sensitivity to second and third generation tyrosine kinase inhibitors. Am. J. Hematol., 2012, 87(11), E125-E128.
[http://dx.doi.org/10.1002/ajh.23338] [PMID: 23044928]
[83]
Lai, A.C.; Toure, M.; Hellerschmied, D.; Salami, J. Jaime, Figueroa, S.; Ko, E. Modular PROTACS design for the degradation of oncogenic BCR‐ABL. Angew. Chem. Int. Ed., 2016, 55(2), 807-810.
[http://dx.doi.org/10.1002/anie.201507634] [PMID: 26593377]
[84]
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]
[85]
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]
[86]
Burslem, G.M.; Schultz, A.R.; Bondeson, D.P.; Eide, C.A.; Savage Stevens, S.L.; Druker, B.J.; Crews, C.M. Targeting BCR-ABL1 in chronic myeloid leukemia by PROTACS-mediated targeted protein degradation. Cancer Res., 2019, 79(18), 4744-4753.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-1236] [PMID: 31311809]
[87]
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]
[88]
Malumbres, M. Cyclin-dependent kinases. Genome Biol., 2014, 15(6), 122.
[http://dx.doi.org/10.1186/gb4184] [PMID: 25180339]
[89]
Dorée, M.; Galas, S. The cyclin-dependent protein kinases and the control of cell division. FASEB J., 1994, 8(14), 1114-1121.
[http://dx.doi.org/10.1096/fasebj.8.14.7958616] [PMID: 7958616]
[90]
Yang, C.; Li, Z.; Bhatt, T.; Dickler, M.; Giri, D.; Scaltriti, M.; Baselga, J.; Rosen, N.; Chandarlapaty, S. Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence. Oncogene, 2017, 36(16), 2255-2264.
[http://dx.doi.org/10.1038/onc.2016.379] [PMID: 27748766]
[91]
Li, Z.; Razavi, P.; Li, Q.; Toy, W.; Liu, B.; Ping, C.; Hsieh, W.; Sanchez-Vega, F.; Brown, D.N.; Da Cruz Paula, A.F.; Morris, L.; Selenica, P.; Eichenberger, E.; Shen, R.; Schultz, N.; Rosen, N.; Scaltriti, M.; Brogi, E.; Baselga, J.; Reis-Filho, J.S.; Chandarlapaty, S. Loss of the FAT1 tumor suppressor promotes resistance to CDK4/6 inhibitors via the hippo pathway. Cancer Cell, 2018, 34(6), 893-905.e8.
[http://dx.doi.org/10.1016/j.ccell.2018.11.006] [PMID: 30537512]
[92]
Allen, B.L.; Taatjes, D.J. The mediator complex: A central integrator of transcription. Nat. Rev. Mol. Cell Biol., 2015, 16(3), 155-166.
[http://dx.doi.org/10.1038/nrm3951] [PMID: 25693131]
[93]
Carlsten, J.O.; Zhu, X.; Gustafsson, C.M. The multitalented mediator complex. Trends Biochem. Sci., 2013, 38(11), 531-537.
[http://dx.doi.org/10.1016/j.tibs.2013.08.007] [PMID: 24074826]
[94]
Schiano, C.; Casamassimi, A.; Rienzo, M. de, Nigris, F.; Sommese, L.; Napoli, C. Involvement of mediator complex in malignancy. Biochim. Biophys. Acta, 2014, 1845(1), 66-83.
[95]
Krystof, V.; Baumli, S.; Fürst, R. Perspective of cyclin-dependent kinase 9 (CDK9) as a drug target. Curr. Pharm. Des., 2012, 18(20), 2883-2890.
[http://dx.doi.org/10.2174/138161212800672750] [PMID: 22571657]
[96]
Zhao, B.; Burgess, K. PROTACs suppression of CDK4/6, crucial kinases for cell cycle regulation in cancer. Chem. Commun. (Camb.), 2019, 55(18), 2704-2707.
[http://dx.doi.org/10.1039/C9CC00163H] [PMID: 30758029]
[97]
Jiang, B.; Wang, E.S.; Donovan, K.A.; Liang, Y.; Fischer, E.S.; Zhang, T.; Gray, N.S. Development of dual and selective degraders of cyclin‐dependent kinases 4 and 6. Angew. Chem. Int. Ed. Engl., 2019, 58(19), 6321-6326.
[http://dx.doi.org/10.1002/anie.201901336] [PMID: 30802347]
[98]
Su, S.; Yang, Z.; Gao, H.; Yang, H.; Zhu, S.; An, Z.; Wang, J.; Li, Q.; Chandarlapaty, S.; Deng, H.; Wu, W.; Rao, Y. Potent and preferential degradation of CDK6 via proteolysis targeting chimera degraders. J. Med. Chem., 2019, 62(16), 7575-7582.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00871] [PMID: 31330105]
[99]
Hatcher, J.M.; Wang, E.S.; Johannessen, L.; Kwiatkowski, N.; Sim, T.; Gray, N.S. Development of highly potent and selective steroidal inhibitors and degraders of CDK8. ACS Med. Chem. Lett., 2018, 9(6), 540-545.
[http://dx.doi.org/10.1021/acsmedchemlett.8b00011] [PMID: 29937979]
[100]
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]
[101]
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]
[102]
Ruvolo, P.P.; Deng, X.; May, W.S. Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia, 2001, 15(4), 515-522.
[http://dx.doi.org/10.1038/sj.leu.2402090] [PMID: 11368354]
[103]
Zhang, X.; Thummuri, D.; He, Y.; Liu, X.; Zhang, P.; Zhou, D.; Zheng, G. Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-XL. Chem. Commun. (Camb.), 2019, 55(98), 14765-14768.
[http://dx.doi.org/10.1039/C9CC07217A] [PMID: 31754664]
[104]
Blombery, P.; Birkinshaw, R.W.; Nguyen, T.; Gong, J.N.; Thompson, E.R.; Xu, Z.; Westerman, D.A.; Czabotar, P.E.; Dickinson, M.; Huang, D.C.S.; Seymour, J.F.; Roberts, A.W. Characterization of a novel venetoclax resistance mutation (BCL2 Phe104Ile) observed in follicular lymphoma. Br. J. Haematol., 2019, 186(6), e188-e191.
[http://dx.doi.org/10.1111/bjh.16069] [PMID: 31234236]
[105]
Wang, Z.; He, N.; Guo, Z.; Niu, C.; Song, T.; Guo, Y.; Cao, K.; Wang, A.; Zhu, J.; Zhang, X.; Zhang, Z. Proteolysis targeting chimeras for the selective degradation of Mcl-1/Bcl-2 derived from nonselective target binding ligands. J. Med. Chem., 2019, 62(17), 8152-8163.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00919] [PMID: 31389699]
[106]
Khan, S.; Zhang, X.; Lv, D.; Zhang, Q.; He, Y.; Zhang, P.; Liu, X.; Thummuri, D.; Yuan, Y.; Wiegand, J.S.; Pei, J.; Zhang, W.; Sharma, A.; McCurdy, C.R.; Kuruvilla, V.M.; Baran, N.; Ferrando, A.A.; Kim, Y.M.; Rogojina, A.; Houghton, P.J.; Huang, G.; Hromas, R.; Konopleva, M.; Zheng, G.; Zhou, D. A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nat. Med., 2019, 25(12), 1938-1947.
[http://dx.doi.org/10.1038/s41591-019-0668-z] [PMID: 31792461]
[107]
Cattoretti, G.; Pasqualucci, L.; Ballon, G.; Tam, W.; Nandula, S.V.; Shen, Q.; Mo, T.; Murty, V.V.; Dalla-Favera, R. Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice. Cancer Cell, 2005, 7(5), 445-455.
[http://dx.doi.org/10.1016/j.ccr.2005.03.037] [PMID: 15894265]
[108]
Dalla-Favera, R.; Gaidano, G. Molecular biology of lymphomas. Can. Princip. Pract Oncol, 2001, 6, 2215-2235.
[109]
Shaffer, A.L.; Yu, X.; He, Y.; Boldrick, J.; Chan, E.P.; Staudt, L.M. BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity, 2000, 13(2), 199-212.
[http://dx.doi.org/10.1016/S1074-7613(00)00020-0] [PMID: 10981963]
[110]
Niu, H.; Cattoretti, G.; Dalla-Favera, R. BCL6 controls the expression of the B7-1/CD80 costimulatory receptor in germinal center B cells. J. Exp. Med., 2003, 198(2), 211-221.
[http://dx.doi.org/10.1084/jem.20021395] [PMID: 12860928]
[111]
Yang, H.; Green, M.R. Epigenetic programing of B-cell lymphoma by BCL6 and its genetic deregulation. Front. Cell Dev. Biol., 2019, 7, 272.
[http://dx.doi.org/10.3389/fcell.2019.00272] [PMID: 31788471]
[112]
McCoull, W.; Cheung, T.; Anderson, E.; Barton, P.; Burgess, J.; Byth, K.; Cao, Q.; Castaldi, M.P.; Chen, H.; Chiarparin, E.; Carbajo, R.J.; Code, E.; Cowan, S.; Davey, P.R.; Ferguson, A.D.; Fillery, S.; Fuller, N.O.; Gao, N.; Hargreaves, D.; Howard, M.R.; Hu, J.; Kawatkar, A.; Kemmitt, P.D.; Leo, E.; Molina, D.M.; O’Connell, N.; Petteruti, P.; Rasmusson, T.; Raubo, P.; Rawlins, P.B.; Ricchiuto, P.; Robb, G.R.; Schenone, M.; Waring, M.J.; Zinda, M.; Fawell, S.; Wilson, D.M. Development of a novel B-cell lymphoma 6 (BCL6) PROTACS to provide insight into small molecule targeting of BCL6. ACS Chem. Biol., 2018, 13(11), 3131-3141.
[http://dx.doi.org/10.1021/acschembio.8b00698] [PMID: 30335946]
[113]
Hallberg, B.; Palmer, R.H. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat. Rev. Cancer, 2013, 13(10), 685-700.
[http://dx.doi.org/10.1038/nrc3580] [PMID: 24060861]
[114]
Holla, V.R.; Elamin, Y.Y.; Bailey, A.M.; Johnson, A.M.; Litzenburger, B.C.; Khotskaya, Y.B.; Sanchez, N.S.; Zeng, J.; Shufean, M.A.; Shaw, K.R.; Mendelsohn, J.; Mills, G.B.; Meric-Bernstam, F.; Simon, G.R. ALK: A tyrosine kinase target for cancer therapy. Cold Spring Harb. Mol. Case Stud., 2017, 3(1), a001115.
[http://dx.doi.org/10.1101/mcs.a001115] [PMID: 28050598]
[115]
De Brouwer, S.; De Preter, K.; Kumps, C.; Zabrocki, P.; Porcu, M.; Westerhout, E.M.; Lakeman, A.; Vandesompele, J.; Hoebeeck, J.; Van Maerken, T.; De Paepe, A.; Laureys, G.; Schulte, J.H.; Schramm, A.; Van Den Broecke, C.; Vermeulen, J.; Van Roy, N.; Beiske, K.; Renard, M.; Noguera, R.; Delattre, O.; Janoueix-Lerosey, I.; Kogner, P.; Martinsson, T.; Nakagawara, A.; Ohira, M.; Caron, H.; Eggert, A.; Cools, J.; Versteeg, R.; Speleman, F. Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification. Clin. Cancer Res., 2010, 16(17), 4353-4362.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2660] [PMID: 20719933]
[116]
Dirks, W.G.; Fähnrich, S.; Lis, Y.; Becker, E.; MacLeod, R.A.; Drexler, H.G. Expression and functional analysis of the anaplastic lymphoma kinase (ALK) gene in tumor cell lines. Int. J. Cancer, 2002, 100(1), 49-56.
[http://dx.doi.org/10.1002/ijc.10435] [PMID: 12115586]
[117]
Lin, J.J.; Riely, G.J.; Shaw, A.T. Targeting ALK: Precision medicine takes on drug resistance. Cancer Discov., 2017, 7(2), 137-155.
[http://dx.doi.org/10.1158/2159-8290.CD-16-1123] [PMID: 28122866]
[118]
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]
[119]
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]
[120]
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]
[121]
Wang, Y.; Han, L.; Liu, F.; Yang, F.; Jiang, X.; Sun, H.; Feng, F.; Xue, J.; Liu, W. Targeted degradation of anaplastic lymphoma kinase by gold nanoparticle-based multi-headed proteolysis targeting chimeras. Colloids Surf. B Biointerfaces, 2020, 188, 110795.
[http://dx.doi.org/10.1016/j.colsurfb.2020.110795] [PMID: 31991291]
[122]
Litchfield, D.W. Protein kinase CK2: Structure, regulation and role in cellular decisions of life and death. Biochem. J., 2003, 369(Pt 1), 1-15.
[http://dx.doi.org/10.1042/bj20021469] [PMID: 12396231]
[123]
Tapia, J.C.; Torres, V.A.; Rodriguez, D.A.; Leyton, L.; Quest, A.F. Casein kinase 2 (CK2) increases survivin expression via enhanced β-catenin-T cell factor/lymphoid enhancer binding factor-dependent transcription. Proc. Natl. Acad. Sci. USA, 2006, 103(41), 15079-15084.
[http://dx.doi.org/10.1073/pnas.0606845103] [PMID: 17005722]
[124]
Chen, H.; Chen, F.; Liu, N.; Wang, X.; Gou, S. Chemically induced degradation of CK2 by proteolysis targeting chimeras based on a ubiquitin-proteasome pathway. Bioorg. Chem., 2018, 81, 536-544.
[http://dx.doi.org/10.1016/j.bioorg.2018.09.005] [PMID: 30245235]
[125]
Mebratu, Y.; Tesfaigzi, Y. How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle, 2009, 8(8), 1168-1175.
[http://dx.doi.org/10.4161/cc.8.8.8147] [PMID: 19282669]
[126]
Meloche, S.; Pouysségur, J. The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene, 2007, 26(22), 3227-3239.
[http://dx.doi.org/10.1038/sj.onc.1210414] [PMID: 17496918]
[127]
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]
[128]
Zachary, I.; Sinnett-Smith, J.; Rozengurt, E. Bombesin, vasopressin, and endothelin stimulation of tyrosine phosphorylation in Swiss 3T3 cells. Identification of a novel tyrosine kinase as a major substrate. J. Biol. Chem., 1992, 267(27), 19031-19034.
[http://dx.doi.org/10.1016/S0021-9258(18)41733-4] [PMID: 1382065]
[129]
van Nimwegen, M.J.; van de Water, B. Focal adhesion kinase: A potential target in cancer therapy. Biochem. Pharmacol., 2007, 73(5), 597-609.
[http://dx.doi.org/10.1016/j.bcp.2006.08.011] [PMID: 16997283]
[130]
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]
[131]
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]
[132]
Cance, W.G.; Kurenova, E.; Marlowe, T.; Golubovskaya, V. Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics. Sci. Signal., 2013, 6(268), pe10.
[http://dx.doi.org/10.1126/scisignal.2004021] [PMID: 23532331]
[133]
Schaller, M.D. Cellular functions of FAK kinases: Insight into molecular mechanisms and novel functions. J. Cell Sci., 2010, 123(Pt 7), 1007-1013.
[http://dx.doi.org/10.1242/jcs.045112] [PMID: 20332118]
[134]
Mitra, S.K.; Hanson, D.A.; Schlaepfer, D.D. Focal adhesion kinase: In command and control of cell motility. Nat. Rev. Mol. Cell Biol., 2005, 6(1), 56-68.
[http://dx.doi.org/10.1038/nrm1549] [PMID: 15688067]
[135]
Kessler, B.E.; Sharma, V.; Zhou, Q.; Jing, X.; Pike, L.A.; Kerege, A.A.; Sams, S.B.; Schweppe, R.E. FAK expression, not kinase activity, is a key mediator of thyroid tumorigenesis and protumorigenic processes. Mol. Cancer Res., 2016, 14(9), 869-882.
[http://dx.doi.org/10.1158/1541-7786.MCR-16-0007] [PMID: 27259715]
[136]
Béraud, C.; Dormoy, V.; Danilin, S.; Lindner, V.; Béthry, A.; Hochane, M.; Coquard, C.; Barthelmebs, M.; Jacqmin, D.; Lang, H.; Massfelder, T. Targeting FAK scaffold functions inhibits human renal cell carcinoma growth. Int. J. Cancer, 2015, 137(7), 1549-1559.
[http://dx.doi.org/10.1002/ijc.29522] [PMID: 25809490]
[137]
Gogate, P.N.; Kurenova, E.V.; Ethirajan, M.; Liao, J.; Yemma, M.; Sen, A.; Pandey, R.K.; Cance, W.G. Targeting the C-terminal focal adhesion kinase scaffold in pancreatic cancer. Cancer Lett., 2014, 353(2), 281-289.
[http://dx.doi.org/10.1016/j.canlet.2014.07.032] [PMID: 25067788]
[138]
Gungor-Ordueri, N.E.; Mruk, D.D.; Wan, H.T.; Wong, E.W.; Celik-Ozenci, C.; Lie, P.P.; Cheng, C.Y. New insights into FAK function and regulation during spermatogenesis. Histol. Histopathol., 2014, 29(8), 977-989.
[PMID: 24578181]
[139]
Cromm, P.M.; Samarasinghe, K.T.G.; Hines, J.; Crews, C.M. Addressing kinase-independent functions of Fak via PROTACS-mediated degradation. J. Am. Chem. Soc., 2018, 140(49), 17019-17026.
[http://dx.doi.org/10.1021/jacs.8b08008] [PMID: 30444612]
[140]
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]
[141]
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]
[142]
Kazi, J.U.; Rönnstrand, L. FMS-like tyrosine kinase 3/FLT3: From basic science to clinical implications. Physiol. Rev., 2019, 99(3), 1433-1466.
[http://dx.doi.org/10.1152/physrev.00029.2018] [PMID: 31066629]
[143]
Armstrong, S.A.; Kung, A.L.; Mabon, M.E.; Silverman, L.B.; Stam, R.W.; Den Boer, M.L.; Pieters, R.; Kersey, J.H.; Sallan, S.E.; Fletcher, J.A.; Golub, T.R.; Griffin, J.D.; Korsmeyer, S.J. Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell, 2003, 3(2), 173-183.
[http://dx.doi.org/10.1016/S1535-6108(03)00003-5] [PMID: 12620411]
[144]
Kuchenbauer, F.; Kern, W.; Schoch, C.; Kohlmann, A.; Hiddemann, W.; Haferlach, T.; Schnittger, S. Detailed analysis of FLT3 expression levels in acute myeloid leukemia. Haematologica, 2005, 90(12), 1617-1625.
[PMID: 16330434]
[145]
Huang, H.T.; Dobrovolsky, D.; Paulk, J.; Yang, G.; Weisberg, E.L.; Doctor, Z.M. A chemoproteomic approach to query the degradable kinome using a multi-kinase degrader. Cell Chem. Biol., 2018, 25(1), 88-99.
[146]
Burslem, G.M.; Song, J.; Chen, X.; Hines, J.; Crews, C.M. Enhancing antiproliferative activity and selectivity of a FLT-3 inhibitor by proteolysis targeting chimera conversion. J. Am. Chem. Soc., 2018, 140(48), 16428-16432.
[http://dx.doi.org/10.1021/jacs.8b10320] [PMID: 30427680]
[147]
Seto, E.; Yoshida, M. Erasers of histone acetylation: The histone deacetylase enzymes. Cold Spring Harb. Perspect. Biol., 2014, 6(4), a018713.
[http://dx.doi.org/10.1101/cshperspect.a018713] [PMID: 24691964]
[148]
Valenzuela-Fernández, A.; Cabrero, J.R.; Serrador, J.M.; Sánchez-Madrid, F. HDAC6: A key regulator of cytoskeleton, cell migration and cell-cell interactions. Cell Biol. (Henderson NV), 2008, 18(6), 291-297.
[http://dx.doi.org/10.1016/j.tcb.2008.04.003] [PMID: 18472263]
[149]
Boyault, C.; Gilquin, B.; Zhang, Y.; Rybin, V.; Garman, E.; Meyer-Klaucke, W.; Matthias, P.; Müller, C.W.; Khochbin, S. HDAC6-p97/VCP controlled polyubiquitin chain turnover. EMBO J., 2006, 25(14), 3357-3366.
[http://dx.doi.org/10.1038/sj.emboj.7601210] [PMID: 16810319]
[150]
Hubbert, C.; Guardiola, A.; Shao, R.; Kawaguchi, Y.; Ito, A.; Nixon, A.; Yoshida, M.; Wang, X.F.; Yao, T.P. HDAC6 is a microtubule-associated deacetylase. Nature, 2002, 417(6887), 455-458.
[http://dx.doi.org/10.1038/417455a] [PMID: 12024216]
[151]
Boyault, C.; Sadoul, K.; Pabion, M.; Khochbin, S. HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination. Oncogene, 2007, 26(37), 5468-5476.
[http://dx.doi.org/10.1038/sj.onc.1210614] [PMID: 17694087]
[152]
Batchu, S.N.; Brijmohan, A.S.; Advani, A. The therapeutic hope for HDAC6 inhibitors in malignancy and chronic disease. Clin. Sci. (Lond.), 2016, 130(12), 987-1003.
[http://dx.doi.org/10.1042/CS20160084] [PMID: 27154743]
[153]
Yang, K.; Song, Y.; Xie, H.; Wu, H.; Wu, Y-T.; Leisten, E.D.; Tang, W. Development of the first small molecule histone deacetylase 6 (HDAC6) degraders. Bioorg. Med. Chem. Lett., 2018, 28(14), 2493-2497.
[http://dx.doi.org/10.1016/j.bmcl.2018.05.057] [PMID: 29871848]
[154]
Wu, H.; Yang, K.; Zhang, Z.; Leisten, E.D.; Li, Z.; Xie, H.; Liu, J.; Smith, K.A.; Novakova, Z.; Barinka, C.; Tang, W. Development of multifunctional histone deacetylase 6 degraders with potent antimyeloma activity. J. Med. Chem., 2019, 62(15), 7042-7057.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00516] [PMID: 31271281]
[155]
An, Z.; Lv, W.; Su, S.; Wu, W.; Rao, Y. Developing potent PROTACs tools for selective degradation of HDAC6 protein. Protein Cell, 2019, 10(8), 606-609.
[http://dx.doi.org/10.1007/s13238-018-0602-z] [PMID: 30603959]
[156]
Wang, L.; Kwak, J.; Kim, S.; He, Y.; Choi, M. TGF-beta 1 stimulates vascular endothelial growth factor (VEGF) 164 via mitogen-activated protein kinase kinase 3 (MKK3)-p38alpha and p38delta MAPK dependent pathway in murine mesangial cells. J. Biol. Chem., 2004, 279, 33213-33219.
[http://dx.doi.org/10.1074/jbc.M403758200] [PMID: 15143069]
[157]
Wang, L.; Ma, R.; Flavell, R.A.; Choi, M.E. Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for activation of p38α and p38δ MAPK isoforms by TGF-β 1 in murine mesangial cells. J. Biol. Chem., 2002, 277(49), 47257-47262.
[http://dx.doi.org/10.1074/jbc.M208573200] [PMID: 12374793]
[158]
Kim, S.I.; Kwak, J.H.; Zachariah, M.; He, Y.; Wang, L.; Choi, M.E. TGF-beta-activated kinase 1 and TAK1-binding protein 1 cooperate to mediate TGF-beta1-induced MKK3-p38 MAPK activation and stimulation of type I collagen. Am. J. Physiol. Renal Physiol., 2007, 292(5), F1471-F1478.
[http://dx.doi.org/10.1152/ajprenal.00485.2006] [PMID: 17299140]
[159]
Smith, B.E.; Wang, S.L.; Jaime-Figueroa, S.; Harbin, A.; Wang, J.; Hamman, B.D. Differential PROTACS substrate specificity dictated by orientation of recruited E3 ligase. Nat. Comms, 2019, 10(1), 1-13.
[http://dx.doi.org/10.1038/s41467-018-08027-7]
[160]
Arcaro, A.; Guerreiro, A.S. The phosphoinositide 3-kinase pathway in human cancer: Genetic alterations and therapeutic implications. Curr. Genomics, 2007, 8(5), 271-306.
[http://dx.doi.org/10.2174/138920207782446160] [PMID: 19384426]
[161]
Maffucci, T.; Cooke, F.T.; Foster, F.M.; Traer, C.J.; Fry, M.J.; Falasca, M. Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. J. Cell Biol., 2005, 169(5), 789-799.
[http://dx.doi.org/10.1083/jcb.200408005] [PMID: 15928202]
[162]
Foster, F.M.; Traer, C.J.; Abraham, S.M.; Fry, M.J. The phosphoinositide (PI) 3-kinase family. J. Cell Sci., 2003, 116(Pt 15), 3037-3040.
[http://dx.doi.org/10.1242/jcs.00609] [PMID: 12829733]
[163]
Yadav, R.R.; Guru, S.K.; Joshi, P.; Mahajan, G.; Mintoo, M.J.; Kumar, V.; Bharate, S.S.; Mondhe, D.M.; Vishwakarma, R.A.; Bhushan, S.; Bharate, S.B. 6-Aryl substituted 4-(4-cyanomethyl) phenylamino quinazolines as a new class of isoform-selective PI3K-alpha inhibitors. Eur. J. Med. Chem., 2016, 122, 731-743.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.006] [PMID: 27479483]
[164]
Li, W.; Gao, C.; Zhao, L.; Yuan, Z.; Chen, Y.; Jiang, Y. Phthalimide conjugations for the degradation of oncogenic PI3K. Eur. J. Med. Chem., 2018, 151, 237-247.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.066] [PMID: 29625382]
[165]
Hugot, J.P.; Chamaillard, M.; Zouali, H.; Lesage, S.; Cézard, J.P.; Belaiche, J.; Almer, S.; Tysk, C.; O’Morain, C.A.; Gassull, M.; Binder, V.; Finkel, Y.; Cortot, A.; Modigliani, R.; Laurent-Puig, P.; Gower-Rousseau, C.; Macry, J.; Colombel, J.F.; Sahbatou, M.; Thomas, G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature, 2001, 411(6837), 599-603.
[http://dx.doi.org/10.1038/35079107] [PMID: 11385576]
[166]
Ogura, Y.; Bonen, D.K.; Inohara, N.; Nicolae, D.L.; Chen, F.F.; Ramos, R.; Britton, H.; Moran, T.; Karaliuskas, R.; Duerr, R.H.; Achkar, J.P.; Brant, S.R.; Bayless, T.M.; Kirschner, B.S.; Hanauer, S.B.; Nuñez, G.; Cho, J.H. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature, 2001, 411(6837), 603-606.
[http://dx.doi.org/10.1038/35079114] [PMID: 11385577]
[167]
Hasegawa, M.; Fujimoto, Y.; Lucas, P.C.; Nakano, H.; Fukase, K.; Núñez, G.; Inohara, N. A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. EMBO J., 2008, 27(2), 373-383.
[http://dx.doi.org/10.1038/sj.emboj.7601962] [PMID: 18079694]
[168]
Heim, V.J.; Stafford, C.A.; Nachbur, U. NOD signaling and cell death. Front. Cell Dev. Biol., 2019, 7, 208.
[http://dx.doi.org/10.3389/fcell.2019.00208] [PMID: 31632962]
[169]
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]
[170]
Murray, J.T.; Cummings, L.A.; Bloomberg, G.B.; Cohen, P. Identification of different specificity requirements between SGK1 and PKBalpha. FEBS Lett., 2005, 579(5), 991-994.
[http://dx.doi.org/10.1016/j.febslet.2004.12.069] [PMID: 15710380]
[171]
Faes, S.; Dormond, O. PI3K and AKT: Unfaithful partners in cancer. Int. J. Mol. Sci., 2015, 16(9), 21138-21152.
[http://dx.doi.org/10.3390/ijms160921138] [PMID: 26404259]
[172]
Malik, N.; Macartney, T.; Hornberger, A.; Anderson, K.E.; Tovell, H.; Prescott, A.R.; Alessi, D.R. Mechanism of activation of SGK3 by growth factors via the Class 1 and Class 3 PI3Ks. Biochem. J., 2018, 475(1), 117-135.
[http://dx.doi.org/10.1042/BCJ20170650] [PMID: 29150437]
[173]
Bago, R.; Malik, N.; Munson, M.J.; Prescott, A.R.; Davies, P.; Sommer, E.; Shpiro, N.; Ward, R.; Cross, D.; Ganley, I.G.; Alessi, D.R. Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase. Biochem. J., 2014, 463(3), 413-427.
[http://dx.doi.org/10.1042/BJ20140889] [PMID: 25177796]
[174]
Tovell, H.; Testa, A.; Zhou, H.; Shpiro, N.; Crafter, C.; Ciulli, A.; Alessi, D.R. Design and characterization of SGK3-PROTACS1, an isoform specific SGK3 kinase PROTACS degrader. ACS Chem. Biol., 2019, 14(9), 2024-2034.
[http://dx.doi.org/10.1021/acschembio.9b00505] [PMID: 31461270]
[175]
Verpooten, D.; Ma, Y.; Hou, S.; Yan, Z.; He, B. Control of TANK-binding kinase 1-mediated signaling by the γ(1)34.5 protein of herpes simplex virus 1. J. Biol. Chem., 2009, 284(2), 1097-1105.
[http://dx.doi.org/10.1074/jbc.M805905200] [PMID: 19010780]
[176]
Clark, K.; Peggie, M.; Plater, L.; Sorcek, R.J.; Young, E.R.; Madwed, J.B.; Hough, J.; McIver, E.G.; Cohen, P. Novel cross-talk within the IKK family controls innate immunity. Biochem. J., 2011, 434(1), 93-104.
[http://dx.doi.org/10.1042/BJ20101701] [PMID: 21138416]
[177]
Hammaker, D.; Boyle, D.L.; Firestein, G.S. Synoviocyte innate immune responses: TANK-binding kinase-1 as a potential therapeutic target in rheumatoid arthritis. Rheumatology (Oxford), 2012, 51(4), 610-618.
[http://dx.doi.org/10.1093/rheumatology/ker154] [PMID: 21613249]
[178]
Barbie, D.A.; Tamayo, P.; Boehm, J.S.; Kim, S.Y.; Moody, S.E.; Dunn, I.F.; Schinzel, A.C.; Sandy, P.; Meylan, E.; Scholl, C.; Fröhling, S.; Chan, E.M.; Sos, M.L.; Michel, K.; Mermel, C.; Silver, S.J.; Weir, B.A.; Reiling, J.H.; Sheng, Q.; Gupta, P.B.; Wadlow, R.C.; Le, H.; Hoersch, S.; Wittner, B.S.; Ramaswamy, S.; Livingston, D.M.; Sabatini, D.M.; Meyerson, M.; Thomas, R.K.; Lander, E.S.; Mesirov, J.P.; Root, D.E.; Gilliland, D.G.; Jacks, T.; Hahn, W.C. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature, 2009, 462(7269), 108-112.
[http://dx.doi.org/10.1038/nature08460] [PMID: 19847166]
[179]
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]
[180]
von der Haar, T.; Gross, J.D.; Wagner, G.; McCarthy, J.E. The mRNA cap-binding protein eIF4E in post-transcriptional gene expression. Nat. Struct. Mol. Biol., 2004, 11(6), 503-511.
[http://dx.doi.org/10.1038/nsmb779] [PMID: 15164008]
[181]
De Benedetti, A.; Graff, J.R. eIF-4E expression and its role in malignancies and metastases. Oncogene, 2004, 23(18), 3189-3199.
[http://dx.doi.org/10.1038/sj.onc.1207545] [PMID: 15094768]
[182]
Rousseau, D.; Kaspar, R.; Rosenwald, I.; Gehrke, L.; Sonenberg, N. Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E. Proc. Natl. Acad. Sci. USA, 1996, 93(3), 1065-1070.
[http://dx.doi.org/10.1073/pnas.93.3.1065] [PMID: 8577715]
[183]
Lazaris-Karatzas, A.; Montine, K.S.; Sonenberg, N. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5′ cap. Nature, 1990, 345(6275), 544-547.
[http://dx.doi.org/10.1038/345544a0] [PMID: 2348862]
[184]
Kaur, T.; Menon, A.; Garner, A.L. Synthesis of 7-benzylguanosine cap-analogue conjugates for eIF4E targeted degradation. Eur. J. Med. Chem., 2019, 166, 339-350.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.080] [PMID: 30735900]
[185]
Herbst, R.S. Review of epidermal growth factor receptor biology. Int. J. Radiat. Oncol. Biol. Phys., 2004, 59(2)(Suppl.), 21-26.
[http://dx.doi.org/10.1016/j.ijrobp.2003.11.041] [PMID: 15142631]
[186]
Herbst, R.S.; Langer, C.J. Eds.; Epidermal growth factor receptors as a target for cancer treatment: The emerging role of IMC-C225 in the treatment of lung and head and neck cancers. Semin. Oncol; Elsevier, 2002.
[187]
Slamon, D.J.; Clark, G.M.; Wong, S.G.; Levin, W.J.; Ullrich, A.; McGuire, W.L. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 1987, 235(4785), 177-182.
[188]
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.; Crew, A.P.; Hines, J.; Crews, C.M. The advantages of targeted protein degradation over inhibition: An RTK case study. Cell Chem. Biol., 2018, 25(1), 67-77.e3.
[http://dx.doi.org/10.1016/j.chembiol.2017.09.009] [PMID: 29129716]
[189]
Zameitat, E.; Freymark, G.; Dietz, C.D.; Löffler, M.; Bölker, M. Functional expression of human dihydroorotate dehydrogenase (DHODH) in pyr4 mutants of ustilago maydis allows target validation of DHODH inhibitors in vivo. Appl. Environ. Microbiol., 2007, 73(10), 3371-3379.
[http://dx.doi.org/10.1128/AEM.02569-06] [PMID: 17369345]
[190]
Christopherson, R.I.; Lyons, S.D.; Wilson, P.K. Inhibitors of de novo nucleotide biosynthesis as drugs. Acc. Chem. Res., 2002, 35(11), 961-971.
[http://dx.doi.org/10.1021/ar0000509] [PMID: 12437321]
[191]
Madak, J.T.; Cuthbertson, C.R.; Chen, W.; Showalter, H.D.; Neamati, N. Design, synthesis, and characterization of brequinar conjugates as probes to study DHODH inhibition. Chemistry, 2017, 23(56), 13875-13878.
[http://dx.doi.org/10.1002/chem.201702999]
[192]
Ma, P.C.; Maulik, G.; Christensen, J.; Salgia, R. c-Met: Structure, functions and potential for therapeutic inhibition. Cancer Metastasis Rev., 2003, 22(4), 309-325.
[http://dx.doi.org/10.1023/A:1023768811842] [PMID: 12884908]
[193]
Huh, C-G.; Factor, V.M.; Sánchez, A.; Uchida, K.; Conner, E.A.; Thorgeirsson, S.S. Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc. Natl. Acad. Sci. USA, 2004, 101(13), 4477-4482.
[http://dx.doi.org/10.1073/pnas.0306068101] [PMID: 15070743]
[194]
Martens, T.; Schmidt, N-O.; Eckerich, C.; Fillbrandt, R.; Merchant, M.; Schwall, R.; Westphal, M.; Lamszus, K. A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo. Clin. Cancer Res., 2006, 12(20 Pt 1), 6144-6152.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-1418] [PMID: 17062691]
[195]
Bondeson, D.P.; Smith, B.E.; Burslem, G.M.; Buhimschi, A.D.; Hines, J.; Jaime-Figueroa, S. Lessons in PROTACS design from selective degradation with a promiscuous warhead. Cell Chem. Biol., 2018, 25(1), 78-87.
[http://dx.doi.org/10.1016/j.chembiol.2017.09.010]
[196]
Vassilev, L.T.; Vu, B.T.; Graves, B.; Carvajal, D.; Podlaski, F.; Filipovic, Z.; Kong, N.; Kammlott, U.; Lukacs, C.; Klein, C.; Fotouhi, N.; Liu, E.A. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 2004, 303(5659), 844-848.
[http://dx.doi.org/10.1126/science.1092472] [PMID: 14704432]
[197]
Zhao, Y.; Aguilar, A.; Bernard, D.; Wang, S. Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment. J. Med. Chem., 2015, 58(3), 1038-1052.
[http://dx.doi.org/10.1021/jm501092z] [PMID: 25396320]
[198]
Ray-Coquard, I.; Blay, J-Y.; Italiano, A.; Le Cesne, A.; Penel, N.; Zhi, J.; Heil, F.; Rueger, R.; Graves, B.; Ding, M.; Geho, D.; Middleton, S.A.; Vassilev, L.T.; Nichols, G.L.; Bui, B.N. Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: An exploratory proof-of-mechanism study. Lancet Oncol., 2012, 13(11), 1133-1140.
[http://dx.doi.org/10.1016/S1470-2045(12)70474-6] [PMID: 23084521]
[199]
Ravandi, F.; Gojo, I.; Patnaik, M.M.; Minden, M.D.; Kantarjian, H.; Johnson-Levonas, A.O.; Fancourt, C.; Lam, R.; Jones, M.B.; Knox, C.D.; Rose, S.; Patel, P.S.; Tibes, R. A phase I trial of the human double minute 2 inhibitor (MK-8242) in patients with refractory/recurrent acute myelogenous leukemia (AML). Leuk. Res., 2016, 48, 92-100.
[http://dx.doi.org/10.1016/j.leukres.2016.07.004] [PMID: 27544076]
[200]
Iancu-Rubin, C.; Mosoyan, G.; Glenn, K.; Gordon, R.E.; Nichols, G.L.; Hoffman, R. Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis. Exp. Hematol., 2014, 42(2), 137-145.
[201]
Li, Y.; Yang, J.; Aguilar, A.; McEachern, D.; Przybranowski, S.; Liu, L. Discovery of MD-224 as a first-in-class, highly potent and efficacious PROTACS MDM2 degrader capable of achieving complete and durable tumor regression. J. Med. Chem., 2019, 62(2), 448.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00909] [PMID: 30525597]
[202]
Yang, J.; Li, Y.; Aguilar, A.; Liu, Z.; Yang, C-Y.; Wang, S. Simple structural modifications converting a bona fide MDM2 PROTACS degrader into a molecular glue molecule: A cautionary tale in the design of PROTACS degraders. J. Med. Chem., 2019, 62(21), 9471-9487.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00846] [PMID: 31560543]
[203]
Wang, B.; Wu, S.; Liu, J.; Yang, K.; Xie, H.; Tang, W. Development of selective small molecule MDM2 degraders based on nutlin. Eur. J. Med. Chem., 2019, 176, 476-491.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.046] [PMID: 31128449]
[204]
Hines, J.; Lartigue, S.; Dong, H.; Qian, Y.; Crews, C.M. MDM2-recruiting PROTACS offers superior, synergistic antiproliferative activity via simultaneous degradation of BRD4 and stabilization of p53. Cancer Res., 2019, 79(1), 251-262.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2918] [PMID: 30385614]
[205]
Liu, F.; Rehmani, I.; Esaki, S.; Fu, R.; Chen, L.; de Serrano, V.; Liu, A. Pirin is an iron-dependent redox regulator of NF-κ. B. Proc. Natl. Acad. Sci. USA, 2013, 110(24), 9722-9727.
[http://dx.doi.org/10.1073/pnas.1221743110] [PMID: 23716661]
[206]
Wendler, W.M.; Kremmer, E.; Förster, R.; Winnacker, E-L. Identification of pirin, a novel highly conserved nuclear protein. J. Biol. Chem., 1997, 272(13), 8482-8489.
[http://dx.doi.org/10.1074/jbc.272.13.8482] [PMID: 9079676]
[207]
Pang, H.; Bartlam, M.; Zeng, Q.; Miyatake, H.; Hisano, T.; Miki, K.; Wong, L.L.; Gao, G.F.; Rao, Z. Crystal structure of human pirin: An iron-binding nuclear protein and transcription cofactor. J. Biol. Chem., 2004, 279(2), 1491-1498.
[http://dx.doi.org/10.1074/jbc.M310022200] [PMID: 14573596]
[208]
Chessum, N.E.A.; Sharp, S.Y.; Caldwell, J.J.; Pasqua, A.E.; Wilding, B.; Colombano, G.; Collins, I.; Ozer, B.; Richards, M.; Rowlands, M.; Stubbs, M.; Burke, R.; McAndrew, P.C.; Clarke, P.A.; Workman, P.; Cheeseman, M.D.; Jones, K. Demonstrating in-cell target engagement using a pirin protein degradation probe (CCT367766). J. Med. Chem., 2018, 61(3), 918-933.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01406] [PMID: 29240418]
[209]
Ferrari, K.J.; Scelfo, A.; Jammula, S.; Cuomo, A.; Barozzi, I.; Stützer, A.; Fischle, W.; Bonaldi, T.; Pasini, D. Polycomb-dependent H3K27me1 and H3K27me2 regulate active transcription and enhancer fidelity. Mol. Cell, 2014, 53(1), 49-62.
[http://dx.doi.org/10.1016/j.molcel.2013.10.030] [PMID: 24289921]
[210]
Margueron, R.; Reinberg, D. The Polycomb complex PRC2 and its mark in life. Nature, 2011, 469(7330), 343-349.
[http://dx.doi.org/10.1038/nature09784] [PMID: 21248841]
[211]
Veneti, Z.; Gkouskou, K.K.; Eliopoulos, A.G. Polycomb repressor complex 2 in genomic instability and cancer. Int. J. Mol. Sci., 2017, 18(8), 1657.
[http://dx.doi.org/10.3390/ijms18081657] [PMID: 28758948]
[212]
McCabe, M.T.; Ott, H.M.; Ganji, G.; Korenchuk, S.; Thompson, C.; Van Aller, G.S.; Liu, Y.; Graves, A.P.; Della Pietra, A., III; Diaz, E.; LaFrance, L.V.; Mellinger, M.; Duquenne, C.; Tian, X.; Kruger, R.G.; McHugh, C.F.; Brandt, M.; Miller, W.H.; Dhanak, D.; Verma, S.K.; Tummino, P.J.; Creasy, C.L. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature, 2012, 492(7427), 108-112.
[http://dx.doi.org/10.1038/nature11606] [PMID: 23051747]
[213]
Potjewyd, F.; Turner, A.W.; Beri, J.; Rectenwald, J.M.; Norris-Drouin, J.L.; Cholensky, S.H.; Margolis, D.M.; Pearce, K.H.; Herring, L.E.; James, L.I. Degradation of polycomb repressive complex 2 with an EED-targeted bivalent chemical degrader. Cell Chem. Biol., 2020, 27(1), 47-56.e15.
[http://dx.doi.org/10.1016/j.chembiol.2019.11.006] [PMID: 31831267]
[214]
Haura, E.B.; Turkson, J.; Jove, R. Mechanisms of disease: Insights into the emerging role of signal transducers and activators of transcription in cancer. Nat. Clin. Pract. Oncol., 2005, 2(6), 315-324.
[http://dx.doi.org/10.1038/ncponc0195] [PMID: 16264989]
[215]
Yu, H.; Jove, R. The STATs of cancer-new molecular targets come of age. Nat. Rev. Cancer, 2004, 4(2), 97-105.
[http://dx.doi.org/10.1038/nrc1275] [PMID: 14964307]
[216]
Zhao, C.; Li, H.; Lin, H-J.; Yang, S.; Lin, J.; Liang, G. Feedback activation of STAT3 as a cancer drug-resistance mechanism. Trends Pharmacol. Sci., 2016, 37(1), 47-61.
[http://dx.doi.org/10.1016/j.tips.2015.10.001] [PMID: 26576830]
[217]
Johnson, D.E.; O’Keefe, R.A.; Grandis, J.R. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat. Rev. Clin. Oncol., 2018, 15(4), 234-248.
[http://dx.doi.org/10.1038/nrclinonc.2018.8] [PMID: 29405201]
[218]
Yang, J.; Stark, G.R. Roles of unphosphorylated STATs in signaling. Cell Res., 2008, 18(4), 443-451.
[http://dx.doi.org/10.1038/cr.2008.41] [PMID: 18364677]
[219]
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), 498-511.e17.
[http://dx.doi.org/10.1016/j.ccell.2019.10.002] [PMID: 31715132]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy