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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

Targeted Protein Degradation: An Emerging Therapeutic Strategy in Cancer

Author(s): Samir H. Barghout*

Volume 21, Issue 2, 2021

Published on: 09 April, 2020

Page: [214 - 230] Pages: 17

DOI: 10.2174/1871520620666200410082652

Price: $65


Drug discovery in the scope of cancer therapy has been focused on conventional agents that nonselectively induce DNA damage or selectively inhibit the activity of key oncogenic molecules without affecting their protein levels. An emerging therapeutic strategy that garnered attention in recent years is the induction of Targeted Protein Degradation (TPD) of cellular targets by hijacking the intracellular proteolysis machinery. This novel approach offers several advantages over conventional inhibitors and introduces a paradigm shift in several pharmacological aspects of drug therapy. While TPD has been found to be the major mode of action of clinically approved anticancer agents such as fulvestrant and thalidomide, recent years have witnessed systematic endeavors to expand the repertoire of proteins amenable to therapeutic ablation by TPD. Such endeavors have led to three major classes of agents that induce protein degradation, including molecular glues, Proteolysis Targeting Chimeras (PROTACs) and Hydrophobic Tag (HyT)-based degraders. Here, we briefly highlight agents in these classes and key advances made in the field with a focus on clinical translation in cancer therapy.

Keywords: PROTAC, hydrophobic tag, molecular glue, targeted protein degradation, thalidomide, fulvestrant, cancer therapy, ubiquitin, proteasome, IMiD.

Graphical Abstract
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: the next generation. Cell, 2011, 144(5), 646-674.
[] [PMID: 21376230]
Vogelstein, B.; Papadopoulos, N.; Velculescu, V.E.; Zhou, S.; Diaz, L.A., Jr; Kinzler, K.W. Cancer genome landscapes. Science, 2013, 339(6127), 1546-1558.
[] [PMID: 23539594]
Luo, J.; Solimini, N.L.; Elledge, S.J. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell, 2009, 136(5), 823-837.
[]] [PMID: 19269363]
Dobbelstein, M.; Moll, U. Targeting tumour-supportive cellular machineries in anticancer drug development. Nat. Rev. Drug Discov., 2014, 13(3), 179-196.
[] [PMID: 24577400]
Lazo, J.S.; Sharlow, E.R. Drugging undruggable molecular cancer targets. Annu. Rev. Pharmacol. Toxicol., 2016, 56, 23-40.
[] [PMID: 26527069]
Lai, A.C.; Crews, C.M. Induced protein degradation: an emerging drug discovery paradigm. Nat. Rev. Drug Discov., 2017, 16(2), 101-114.
[] [PMID: 27885283]
Mayor-Ruiz, C.; Winter, G.E. Identification and characterization of cancer vulnerabilities via targeted protein degradation. Drug Discov. Today. Technol., 2019, 31, 81-90.
[] [PMID: 31200863]
Salami, J.; Crews, C.M. Waste disposal-an attractive strategy for cancer therapy. Science, 2017, 355(6330), 1163-1167.
[] [PMID: 28302825]
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.
[] [PMID: 31666732]
Cromm, P.M.; Crews, C.M. Targeted protein degradation: from Chemical biology to drug discovery. Cell Chem. Biol., 2017, 24(9), 1181-1190.
[] [PMID: 28648379]
Chamberlain, P.P.; Hamann, L.G. Development of targeted protein degradation therapeutics. Nat. Chem. Biol., 2019, 15(10), 937-944.
[] [PMID: 31527835]
Paiva, S.L.; Crews, C.M. Targeted protein degradation: elements of PROTAC design. Curr. Opin. Chem. Biol., 2019, 50, 111-119.
[] [PMID: 31004963]
Klaips, C.L.; Jayaraj, G.G.; Hartl, F.U. Pathways of cellular proteostasis in aging and disease. J. Cell Biol., 2018, 217(1), 51-63.
[] [PMID: 29127110]
Hoeller, D.; Dikic, I. Targeting the ubiquitin system in cancer therapy. Nature, 2009, 458(7237), 438-444.
[] [PMID: 19325623]
Galluzzi, L.; Bravo-San Pedro, J.M.; Levine, B.; Green, D.R.; Kroemer, G. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat. Rev. Drug Discov., 2017, 16(7), 487-511.
[] [PMID: 28529316]
Korolchuk, V.I.; Menzies, F.M.; Rubinsztein, D.C. Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems. FEBS Lett., 2010, 584(7), 1393-1398.
[] [PMID: 20040365]
Bedford, L.; Lowe, J.; Dick, L.R.; Mayer, R.J.; Brownell, J.E. Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets. Nat. Rev. Drug Discov., 2011, 10(1), 29-46.
[] [PMID: 21151032]
Bondeson, D.P.; Crews, C.M. Targeted protein degradation by small molecules. Annu. Rev. Pharmacol. Toxicol., 2017, 57, 107-123.
[] [PMID: 27732798]
Hyer, M.L.; Milhollen, M.A.; Ciavarri, J.; Fleming, P.; Traore, T.; Sappal, D.; Huck, J.; Shi, J.; Gavin, J.; Brownell, J.; Yang, Y.; Stringer, B.; Griffin, R.; Bruzzese, F.; Soucy, T.; Duffy, J.; Rabino, C.; Riceberg, J.; Hoar, K.; Lublinsky, A.; Menon, S.; Sintchak, M.; Bump, N.; Pulukuri, S.M.; Langston, S.; Tirrell, S.; Kuranda, M.; Veiby, P.; Newcomb, J.; Li, P.; Wu, J.T.; Powe, J.; Dick, L.R.; Greenspan, P.; Galvin, K.; Manfredi, M.; Claiborne, C.; Amidon, B.S.; Bence, N.F. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment. Nat. Med., 2018, 24(2), 186-193.
[] [PMID: 29334375]
Barghout, S.H.; Patel, P.S.; Wang, X.; Xu, G.W.; Kavanagh, S.; Halgas, O.; Zarabi, S.F.; Gronda, M.; Hurren, R.; Jeyaraju, D.V.; MacLean, N.; Brennan, S.; Hyer, M.L.; Berger, A.; Traore, T.; Milhollen, M.; Smith, A.C.; Minden, M.D.; Pai, E.F.; Hakem, R.; Schimmer, A.D. Preclinical evaluation of the selective small-molecule UBA1 inhibitor, TAK-243, in acute myeloid leukemia. Leukemia, 2019, 33(1), 37-51.
[] [PMID: 29884901]
Soucy, T.A.; Smith, P.G.; Milhollen, M.A.; Berger, A.J.; Gavin, J.M.; Adhikari, S.; Brownell, J.E.; Burke, K.E.; Cardin, D.P.; Critchley, S.; Cullis, C.A.; Doucette, A.; Garnsey, J.J.; Gaulin, J.L.; Gershman, R.E.; Lublinsky, A.R.; McDonald, A.; Mizutani, H.; Narayanan, U.; Olhava, E.J.; Peluso, S.; Rezaei, M.; Sintchak, M.D.; Talreja, T.; Thomas, M.P.; Traore, T.; Vyskocil, S.; Weatherhead, G.S.; Yu, J.; Zhang, J.; Dick, L.R.; Claiborne, C.F.; Rolfe, M.; Bolen, J.B.; Langston, S.P. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature, 2009, 458(7239), 732-736.
[] [PMID: 19360080]
Pal, A.; Young, M.A.; Donato, N.J. Emerging potential of therapeutic targeting of ubiquitin-specific proteases in the treatment of cancer. Cancer Res., 2014, 74(18), 4955-4966.
[] [PMID: 25172841]
Amaravadi, R.K.; Kimmelman, A.C.; Debnath, J. Targeting autophagy in cancer: Recent advances and future directions. Cancer Discov., 2019, 9(9), 1167-1181.
[] [PMID: 31434711]
Manasanch, E.E.; Orlowski, R.Z. Proteasome inhibitors in cancer therapy. Nat. Rev. Clin. Oncol., 2017, 14(7), 417-433.
[] [PMID: 28117417]
Wang, D.; Ma, L.; Wang, B.; Liu, J.; Wei, W. E3 ubiquitin ligases in cancer and implications for therapies. Cancer Metastasis Rev., 2017, 36(4), 683-702.
[] [PMID: 29043469]
Imming, P.; Sinning, C.; Meyer, A. Drugs, their targets and the nature and number of drug targets. Nat. Rev. Drug Discov., 2006, 5(10), 821-834.
[] [PMID: 17016423]
Grimwood, S.; Hartig, P.R. Target site occupancy: emerging generalizations from clinical and preclinical studies. Pharmacol. Ther., 2009, 122(3), 281-301.
[] [PMID: 19306894]
Burslem, G.M.; Crews, C.M. Small-molecule modulation of protein homeostasis. Chem. Rev., 2017, 117(17), 11269-11301.
[] [PMID: 28777566]
Singhal, S.; Mehta, J.; Desikan, R.; Ayers, D.; Roberson, P.; Eddlemon, P.; Munshi, N.; Anaissie, E.; Wilson, C.; Dhodapkar, M.; Zeddis, J.; Barlogie, B. Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med., 1999, 341(21), 1565-1571.
[] [PMID: 10564685]
Fischer, E.S.; Böhm, K.; Lydeard, J.R.; Yang, H.; Stadler, M.B.; Cavadini, S.; Nagel, J.; Serluca, F.; Acker, V.; Lingaraju, G.M.; Tichkule, R.B.; Schebesta, M.; Forrester, W.C.; Schirle, M.; Hassiepen, U.; Ottl, J.; Hild, M.; Beckwith, R.E.; Harper, J.W.; Jenkins, J.L.; Thomä, N.H. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature, 2014, 512(7512), 49-53.
[] [PMID: 25043012]
Krönke, J.; Udeshi, N.D.; Narla, A.; Grauman, P.; Hurst, S.N.; McConkey, M.; Svinkina, T.; Heckl, D.; Comer, E.; Li, X.; Ciarlo, C.; Hartman, E.; Munshi, N.; Schenone, M.; Schreiber, S.L.; Carr, S.A.; Ebert, B.L. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science, 2014, 343(6168), 301-305.
[] [PMID: 24292625]
Lu, G.; Middleton, R.E.; Sun, H.; Naniong, M.; Ott, C.J.; Mitsiades, C.S.; Wong, K.K.; Bradner, J.E.; Kaelin, W.G. Jr. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science, 2014, 343(6168), 305-309.
[] [PMID: 24292623]
Petzold, G.; Fischer, E.S.; Thomä, N.H. Structural basis of lenalidomide-induced CK1α degradation by the CRL4(CRBN) ubiquitin ligase. Nature, 2016, 532(7597), 127-130.
[] [PMID: 26909574]
Krönke, J.; Fink, E.C.; Hollenbach, P.W.; MacBeth, K.J.; Hurst, S.N.; Udeshi, N.D.; Chamberlain, P.P.; Mani, D.R.; Man, H.W.; Gandhi, A.K.; Svinkina, T.; Schneider, R.K.; McConkey, M.; Järås, M.; Griffiths, E.; Wetzler, M.; Bullinger, L.; Cathers, B.E.; Carr, S.A.; Chopra, R.; Ebert, B.L. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature, 2015, 523(7559), 183-188.
[] [PMID: 26131937]
Ruan, J.; Martin, P.; Shah, B.; Schuster, S.J.; Smith, S.M.; Furman, R.R.; Christos, P.; Rodriguez, A.; Svoboda, J.; Lewis, J.; Katz, O.; Coleman, M.; Leonard, J.P. Lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma. N. Engl. J. Med., 2015, 373(19), 1835-1844.
[] [PMID: 26535512]
Moros, A.; Bustany, S.; Cahu, J.; Saborit-Villarroya, I.; Martinez, A.; Colomer, D.; Sola, B.; Roue, G. Antitumoral activity of lenalidomide in in vitro and in vivo models of mantle cell lymphoma involves the destabilization of cyclin D1/p27KIP1 complexes. Clin. Cancer Res., 2014, 20(2), 393-403.
Wang, M.; Fayad, L.; Wagner-Bartak, N.; Zhang, L.; Hagemeister, F.; Neelapu, S.S.; Samaniego, F.; McLaughlin, P.; Fanale, M.; Younes, A.; Cabanillas, F.; Fowler, N.; Newberry, K.J.; Sun, L.; Young, K.H.; Champlin, R.; Kwak, L.; Feng, L.; Badillo, M.; Bejarano, M.; Hartig, K.; Chen, W.; Chen, Y.; Byrne, C.; Bell, N.; Zeldis, J.; Romaguera, J. Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Lancet Oncol., 2012, 13(7), 716-723.
[] [PMID: 22677155]
Miguel, J.S.; Weisel, K.; Moreau, P.; Lacy, M.; Song, K.; Delforge, M.; Karlin, L.; Goldschmidt, H.; Banos, A.; Oriol, A.; Alegre, A.; Chen, C.; Cavo, M.; Garderet, L.; Ivanova, V.; Martinez-Lopez, J.; Belch, A.; Palumbo, A.; Schey, S.; Sonneveld, P.; Yu, X.; Sternas, L.; Jacques, C.; Zaki, M.; Dimopoulos, M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol., 2013, 14(11), 1055-1066.
[] [PMID: 24007748]
Dimopoulos, M.A.; Dytfeld, D.; Grosicki, S.; Moreau, P.; Takezako, N.; Hori, M.; Leleu, X.; LeBlanc, R.; Suzuki, K.; Raab, M.S.; Richardson, P.G.; Popa McKiver, M.; Jou, Y.M.; Shelat, S.G.; Robbins, M.; Rafferty, B.; San-Miguel, J. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N. Engl. J. Med., 2018, 379(19), 1811-1822.
[] [PMID: 30403938]
Attal, M.; Richardson, P.G.; Rajkumar, S.V.; San-Miguel, J.; Beksac, M.; Spicka, I.; Leleu, X.; Schjesvold, F.; Moreau, P.; Dimopoulos, M.A.; Huang, J.S.; Minarik, J.; Cavo, M.; Prince, H.M.; Mace, S.; Corzo, K.P.; Campana, F.; Le-Guennec, S.; Dubin, F.; Anderson, K.C. ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): A randomised, multicentre, open-label, phase 3 study. Lancet, 2019, 394(10214), 2096-2107.
Lopez-Girona, A.; Mendy, D.; Ito, T.; Miller, K.; Gandhi, A.K.; Kang, J.; Karasawa, S.; Carmel, G.; Jackson, P.; Abbasian, M.; Mahmoudi, A.; Cathers, B.; Rychak, E.; Gaidarova, S.; Chen, R.; Schafer, P.H.; Handa, H.; Daniel, T.O.; Evans, J.F.; Chopra, R. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia, 2012, 26(11), 2326-2335.
[] [PMID: 22552008]
Lacy, M.Q.; Hayman, S.R.; Gertz, M.A.; Dispenzieri, A.; Buadi, F.; Kumar, S.; Greipp, P.R.; Lust, J.A.; Russell, S.J.; Dingli, D.; Kyle, R.A.; Fonseca, R.; Bergsagel, P.L.; Roy, V.; Mikhael, J.R.; Stewart, A.K.; Laumann, K.; Allred, J.B.; Mandrekar, S.J.; Rajkumar, S.V. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J. Clin. Oncol., 2009, 27(30), 5008-5014.
[] [PMID: 19720894]
Rasco, D.W.; Papadopoulos, K.P.; Pourdehnad, M.; Gandhi, A.K.; Hagner, P.R.; Li, Y.; Wei, X.; Chopra, R.; Hege, K.; DiMartino, J.; Shih, K. A first-in-human study of novel cereblon modulator avadomide (CC-122) in advanced malignancies. Clin. Cancer Res., 2019, 25(1), 90-98.
Bjorklund, C.C.; Kang, J.; Amatangelo, M.; Polonskaia, A.; Katz, M.; Chiu, H.; Couto, S.; Wang, M.; Ren, Y.; Ortiz, M.; Towfic, F.; Flynt, J.E.; Pierceall, W.; Thakurta, A. Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN. Leukemia, 2020, 34, 1197-1201.
[] [PMID: 31719682]
Matyskiela, M.E.; Zhang, W.; Man, H.W.; Muller, G.; Khambatta, G.; Baculi, F.; Hickman, M.; LeBrun, L.; Pagarigan, B.; Carmel, G.; Lu, C.C.; Lu, G.; Riley, M.; Satoh, Y.; Schafer, P.; Daniel, T.O.; Carmichael, J.; Cathers, B.E.; Chamberlain, P.P. A cereblon modulator (CC-220) with improved degradation of ikaros and aiolos. J. Med. Chem., 2018, 61(2), 535-542.
[] [PMID: 28425720]
Lopez-Girona, A.; Havens, C.G.; Lu, G.; Rychak, E.; Mendy, D.; Gaffney, B.; Surka, C.; Lu, C-C.; Matyskiela, M.; Khambatta, G.; Wong, L.; Hansen, J.; Pierce, D.W.; Cathers, B.E.; Carmichael, J. CC-92480 Is a novel cereblon E3 ligase modulator with enhanced tumoricidal and immunomodulatory activity against sensitive and resistant multiple myeloma cells. Blood, 2019, 134(Suppl. 1), 1812-1812.
Wong, L.; Narla, R.K.; Leisten, J.; Bauer, D.; Groza, M.; Gaffney, B.; Havens, C.G.; Choi, J.; Houston, J.; Lopez-Girona, A.; Hansen, J.; Cathers, B.E.; Carmichael, J.; Pierce, D.W. CC-92480, a novel cereblon E3 ligase modulator, is synergistic with dexamethasone, bortezomib, and daratumumab in multiple myeloma. Blood, 2019, 134(Suppl. 1), 1815-1815.
Matyskiela, M.E.; Lu, G.; Ito, T.; Pagarigan, B.; Lu, C.C.; Miller, K.; Fang, W.; Wang, N.Y.; Nguyen, D.; Houston, J.; Carmel, G.; Tran, T.; Riley, M.; Nosaka, L.; Lander, G.C.; Gaidarova, S.; Xu, S.; Ruchelman, A.L.; Handa, H.; Carmichael, J.; Daniel, T.O.; Cathers, B.E.; Lopez-Girona, A.; Chamberlain, P.P. A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase. Nature, 2016, 535(7611), 252-257.
[] [PMID: 27338790]
Uy, G.L.; Minden, M.D.; Montesinos, P.; DeAngelo, D.J.; Altman, J.K.; Koprivnikar, J.; Vyas, P.; Fløisand, Y.; Belén Vidriales, M.; Gjertsen, B.T.; Esteve, J.; Buchholz, T.J.; Couto, S.; Fan, J.; Hanna, B.; Li, L.; Pierce, D.W.; Hege, K.; Pourdehnad, M.; Zeidan, A.M. Clinical activity of CC-90009, a cereblon E3 ligase modulator and first-in-class GSPT1 degrader, as a single agent in patients with relapsed or refractory Acute Myeloid Leukemia (R/R AML): first results from a phase I dose-finding study. Blood, 2019, 134(Suppl. 1), 232-232.
Lu, G.; Surka, C.; Lu, C-C.; Jang, I.S.; Wang, K.; Rolfe, M. Elucidating the mechanism of action of CC-90009, a novel cereblon E3 ligase modulator, in AML via genome-wide CRISPR screen. Blood, 2019, 134(Suppl. 1), 405-405.
Jin, L.; Mbong, N.; Ng, S.W.K.; Wang, J.C.Y.; Minden, M.D.; Fan, J.; Pierce, D.W.; Pourdehnad, M.; Dick, J.E. A novel cereblon E3 ligase modulator eradicates acute myeloid leukemia stem cells through degradation of translation termination factor GSPT1. Blood, 2019, 134(Suppl. 1), 3940-3940.
Lopez-Girona, A.; Lu, G.; Rychak, E.; Mendy, D.; Lu, C-C.; Rappley, I.; Fontanillo, C.; Cathers, B.E.; Daniel, T.O.; Hansen, J. CC-90009, a novel cereblon E3 ligase modulator, targets GSPT1 for degradation to induce potent tumoricidal activity against Acute Myeloid Leukemia (AML). Blood, 2019, 134(Suppl. 1), 2703-2703.
Fan, J.; Wang, H.; Couto, S.; Yao, T-W.S.; Uy, G.L.; Zeidan, A.M.; Minden, M.D.; Montesinos, P.; DeAngelo, D.J.; Altman, J.K.; Koprivnikar, J.; Vyas, P.; Fløisand, Y.; Belén Vidriales, M.; Gjertsen, B.T.; Buchholz, T.J.; Pourdehnad, M.; Pierce, D.W. Pharmacodynamic responses to CC-90009, a novel cereblon E3 ligase modulator, in a phase I dose-escalation study in relapsed or refractory Acute Myeloid Leukemia (R/R AML). Blood, 2019, 134(Suppl. 1), 2547-2547.
Yang, J.; Li, Y.; Aguilar, A.; Liu, Z.; Yang, C.Y.; Wang, S. Simple structural modifications converting a bona fide MDM2 PROTAC degrader into a molecular glue molecule: A cautionary tale in the design of PROTAC degraders. J. Med. Chem., 2019, 62(21), 9471-9487.
[] [PMID: 31560543]
Bussiere, D.E.; Xie, L.; Srinivas, H.; Shu, W.; Burke, A.; Be, C.; Zhao, J.; Godbole, A.; King, D.; Karki, R.G.; Hornak, V.; Xu, F.; Cobb, J.; Carte, N.; Frank, A.O.; Frommlet, A.; Graff, P.; Knapp, M.; Fazal, A.; Okram, B.; Jiang, S.; Michellys, P-Y.; Beckwith, R.; Voshol, H.; Wiesmann, C.; Solomon, J.; Paulk, J. The structural basis of indisulam-mediated recruitment of RBM39 to the DCAF15-DDB1-DDA1 E3 ligase complex. Nat. Chem. Biol., 2020, 16, 15-23.
Han, T.; Goralski, M.; Gaskill, N.; Capota, E.; Kim, J.; Ting, T.C.; Xie, Y.; Williams, N.S.; Nijhawan, D. Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science, 2017, 356(6336)eaal3755
[]] [PMID: 28302793]
Faust, T.B.; Yoon, H.; Nowak, R.P.; Donovan, K.A.; Li, Z.; Cai, Q.; Eleuteri, N.A.; Zhang, T.; Gray, N.S.; Fischer, E.S. Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat. Chem. Biol., 2020, 16, 7-14.
[PMID: 31686031]
Uehara, T.; Minoshima, Y.; Sagane, K.; Sugi, N.H.; Mitsuhashi, K.O.; Yamamoto, N.; Kamiyama, H.; Takahashi, K.; Kotake, Y.; Uesugi, M.; Yokoi, A.; Inoue, A.; Yoshida, T.; Mabuchi, M.; Tanaka, A.; Owa, T. Selective degradation of splicing factor CAPERα by anticancer sulfonamides. Nat. Chem. Biol., 2017, 13(6), 675-680.
[] [PMID: 28437394]
Du, X.; Volkov, O.A.; Czerwinski, R.M.; Tan, H.; Huerta, C.; Morton, E.R.; Rizzi, J.P.; Wehn, P.M.; Xu, R.; Nijhawan, D.; Wallace, E.M. Structural basis and kinetic pathway of RBM39 recruitment to DCAF15 by a sulfonamide molecular glue E7820. Structure, 2019, 27(11), 1625-1633.e3.
Mita, M.; Kelly, K.R.; Mita, A.; Ricart, A.D.; Romero, O.; Tolcher, A.; Hook, L.; Okereke, C.; Krivelevich, I.; Rossignol, D.P.; Giles, F.J.; Rowinsky, E.K.; Takimoto, C. Phase I study of E7820, an oral inhibitor of integrin alpha-2 expression with antiangiogenic properties, in patients with advanced malignancies. Clin. Cancer Res., 2011, 17(1), 193-200.
Semba, T.; Funahashi, Y.; Ono, N.; Yamamoto, Y.; Sugi, N.H.; Asada, M.; Yoshimatsu, K.; Wakabayashi, T. An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker. Clin. Cancer Res., 2004, 10(4), 1430-1438.
Funahashi, Y.; Sugi, N.H.; Semba, T.; Yamamoto, Y.; Hamaoka, S.; Tsukahara-Tamai, N.; Ozawa, Y.; Tsuruoka, A.; Nara, K.; Takahashi, K.; Okabe, T.; Kamata, J.; Owa, T.; Ueda, N.; Haneda, T.; Yonaga, M.; Yoshimatsu, K.; Wakabayashi, T. Sulfonamide derivative, E7820, is a unique angiogenesis inhibitor suppressing an expression of integrin alpha2 subunit on endothelium. Cancer Res., 2002, 62(21), 6116-6123.
[PMID: 12414636]
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.
[] [PMID: 26051217]
Saenz, D.T.; Fiskus, W.; Qian, Y.; Manshouri, T.; Rajapakshe, K.; Raina, K.; Coleman, K.G.; Crew, A.P.; Shen, A.; Mill, C.P.; Sun, B.; Qiu, P.; Kadia, T.M.; Pemmaraju, N.; DiNardo, C.; Kim, M.S.; Nowak, A.J.; Coarfa, C.; Crews, C.M.; Verstovsek, S.; Bhalla, K.N. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells. Leukemia, 2017, 31(9), 1951-1961.
[] [PMID: 28042144]
Piya, S.; Mu, H.; Bhattacharya, S.; Lorenzi, P.L.; Davis, R.E.; McQueen, T.; Ruvolo, V.; Baran, N.; Wang, Z.; Qian, Y.; Crews, C.M.; Konopleva, M.; Ishizawa, J.; You, M.J.; Kantarjian, H.; Andreeff, M.; Borthakur, G. BETP degradation simultaneously targets acute myelogenous leukemia stem cells and the microenvironment. J. Clin. Invest., 2019, 129(5), 1878-1894.
[] [PMID: 30829648]
Zhang, X.; Lee, H.C.; Shirazi, F.; Baladandayuthapani, V.; Lin, H.; Kuiatse, I.; Wang, H.; Jones, R.J.; Berkova, Z.; Singh, R.K.; Lu, J.; Qian, Y.; Raina, K.; Coleman, K.G.; Crews, C.M.; Li, B.; Wang, H.; Hailemichael, Y.; Thomas, S.K.; Wang, Z.; Davis, R.E.; Orlowski, R.Z. Protein targeting chimeric molecules specific for bromodomain and extra-terminal motif family proteins are active against pre-clinical models of multiple myeloma. Leukemia, 2018, 32(10), 2224-2239.
[] [PMID: 29581547]
Lu, Q.; Ding, X.; Huang, T.; Zhang, S.; Li, Y.; Xu, L.; Chen, G.; Ying, Y.; Wang, Y.; Feng, Z.; Wang, L.; Zou, X. BRD4 degrader ARV-825 produces long-lasting loss of BRD4 protein and exhibits potent efficacy against cholangiocarcinoma cells. Am. J. Transl. Res., 2019, 11(9), 5728-5739.
[PMID: 31632543]
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.
[] [PMID: 25999370]
Bauer, K.; Berger, D.; Zielinski, C.C.; Valent, P.; Grunt, T.W. Hitting two oncogenic machineries in cancer cells: cooperative effects of the multi-kinase inhibitor ponatinib and the BET bromodomain blockers JQ1 or dBET1 on human carcinoma cells. Oncotarget, 2018, 9(41), 26491-26506.
[] [PMID: 29899872]
Winter, G.E.; Mayer, A.; Buckley, D.L.; Erb, M.A.; Roderick, J.E.; Vittori, S.; Reyes, J.M.; di Iulio, J.; Souza, A.; Ott, C.J.; Roberts, J.M.; Zeid, R.; Scott, T.G.; Paulk, J.; Lachance, K.; Olson, C.M.; Dastjerdi, S.; Bauer, S.; Lin, C.Y.; Gray, N.S.; Kelliher, M.A.; Churchman, L.S.; Bradner, J.E. BET bromodomain proteins function as master transcription elongation factors independent of CDK9 recruitment. Mol. Cell, 2017, 67(7), 5-18.e19.
Xu, L.; Chen, Y.; Mayakonda, A.; Koh, L.; Chong, Y.K.; Buckley, D.L.; Sandanaraj, E.; Lim, S.W.; Lin, R.Y.; Ke, X.Y.; Huang, M.L.; Chen, J.; Sun, W.; Wang, L.Z.; Goh, B.C.; Dinh, H.Q.; Kappei, D.; Winter, G.E.; Ding, L.W.; Ang, B.T.; Berman, B.P.; Bradner, J.E.; Tang, C.; Koeffler, H.P. Targetable BET proteins- and E2F1-dependent transcriptional program maintains the malignancy of glioblastoma. Proc. Natl. Acad. Sci. USA, 2018, 115(22), E5086-E5095.
[] [PMID: 29764999]
Hines, J.; Lartigue, S.; Dong, H.; Qian, Y.; Crews, C.M. MDM2-Recruiting PROTAC offers superior, synergistic antiproliferative activity via simultaneous degradation of BRD4 and stabilization of p53. Cancer Res., 2019, 79(1), 251-262.
[] [PMID: 30385614]
Ohoka, N.; Tsuji, G.; Shoda, T.; Fujisato, T.; Kurihara, M.; Demizu, Y.; Naito, M. Development of small molecule chimeras that recruit AhR E3 ligase to target proteins. ACS Chem. Biol., 2019, 14(12), 2822-2832.
[] [PMID: 31580635]
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.
[] [PMID: 27274052]
Mill, C.P.; Fiskus, W.; DiNardo, C.D.; Qian, Y.; Raina, K.; Rajapakshe, K.; Perera, D.; Coarfa, C.; Kadia, T.M.; Khoury, J.D.; Saenz, D.T.; Saenz, D.N.; Illendula, A.; Takahashi, K.; Kornblau, S.M.; Green, M.R.; Futreal, A.P.; Bushweller, J.H.; Crews, C.M.; Bhalla, K.N. RUNX1-targeted therapy for AML expressing somatic or germline mutation in RUNX1. Blood, 2019, 134(1), 59-73.
[] [PMID: 31023702]
Saenz, D.T.; Fiskus, W.; Manshouri, T.; Mill, C.P.; Qian, Y.; Raina, K.; Rajapakshe, K.; Coarfa, C.; Soldi, R.; Bose, P.; Borthakur, G.; Kadia, T.M.; Khoury, J.D.; Masarova, L.; Nowak, A.J.; Sun, B.; Saenz, D.N.; Kornblau, S.M.; Horrigan, S.; Sharma, S.; Qiu, P.; Crews, C.M.; Verstovsek, S.; Bhalla, K.N. Targeting nuclear β-catenin as therapy for post-myeloproliferative neoplasm secondary AML. Leukemia, 2019, 33(6), 1373-1386.
[] [PMID: 30575820]
Sun, B.; Fiskus, W.; Qian, Y.; Rajapakshe, K.; Raina, K.; Coleman, K.G.; Crew, A.P.; Shen, A.; Saenz, D.T.; Mill, C.P.; Nowak, A.J.; Jain, N.; Zhang, L.; Wang, M.; Khoury, J.D.; Coarfa, C.; Crews, C.M.; Bhalla, K.N. BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells. Leukemia, 2018, 32(2), 343-352.
[] [PMID: 28663582]
Jain, N.; Hartert, K.; Tadros, S.; Fiskus, W.; Havranek, O.; Ma, M.C.J.; Bouska, A.; Heavican, T.; Kumar, D.; Deng, Q.; Moore, D.; Pak, C.; Liu, C.L.; Gentles, A.J.; Hartmann, E.; Kridel, R.; Smedby, K.E.; Juliusson, G.; Rosenquist, R.; Gascoyne, R.D.; Rosenwald, A.; Giancotti, F.; Neelapu, S.S.; Westin, J.; Vose, J.M.; Lunning, M.A.; Greiner, T.; Rodig, S.; Iqbal, J.; Alizadeh, A.A.; Davis, R.E.; Bhalla, K.; Green, M.R. Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma. Sci. Transl. Med., 2019, 11(497)eaav5599
[]] [PMID: 31217338]
Shafran, J.S.; Andrieu, G.P.; Györffy, B.; Denis, G.V. BRD4 regulates metastatic potential of castration-resistant prostate cancer through AHNAK. Mol. Cancer Res., 2019, 17(8), 1627-1638.
[] [PMID: 31110158]
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.
[] [PMID: 28339196]
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.
[] [PMID: 31653826]
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.
[] [PMID: 28209615]
Choi, J.E.; Verhaegen, M.E.; Yazdani, S.; Malik, R.; Harms, P.W.; Mangelberger, D.; Tien, J.; Cao, X.; Wang, Y.; Cieślik, M.; Gurkan, J.; Yazdani, M.; Jing, X.; Juckette, K.; Su, F.; Wang, R.; Zhou, B.; Apel, I.J.; Wang, S.; Dlugosz, A.A.; Chinnaiyan, A.M. Characterizing the therapeutic potential of a potent BET degrader in merkel cell carcinoma. Neoplasia, 2019, 21(3), 322-330.
[] [PMID: 30797188]
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.
[] [PMID: 30019901]
Mu, X.; Bai, L.; Xu, Y.; Wang, J.; Lu, H. Protein targeting chimeric molecules specific for dual bromodomain 4 (BRD4) and Polo-like kinase 1 (PLK1) proteins in acute myeloid leukemia cells. Biochem. Biophys. Res. Commun., 2020, 521(4), 833-839.
[PMID: 31708096]
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.
[] [PMID: 30274779]
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.
[] [PMID: 29660984]
Mullard, A. First targeted protein degrader hits the clinic. Nat. Rev. Drug Discov., 2019.
[] [PMID: 30936511]
Neklesa, T.; Snyder, L.B.; Willard, R.R.; Vitale, N.; Pizzano, J.; Gordon, D.A.; Bookbinder, M.; Macaluso, J.; Dong, H.; Ferraro, C.; Wang, G.; Wang, J.; Crews, C.M.; Houston, J.; Crew, A.P.; Taylor, I. ARV-110: An oral androgen receptor PROTAC degrader for prostate cancer. J. Clin. Oncol., 2019, 37(Suppl. 7), 259-259.
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.; Crew, A.P.; Taylor, I. Abstract 5236: ARV-110: An androgen receptor PROTAC degrader for prostate cancer. Cancer Res., 2018, 78(13), 5236-5236.
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.
[] [PMID: 30629437]
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, 100.
[] [PMID: 30271980]
Flanagan, J.; Qian, Y.; Gough, S.; Andreoli, M.; Bookbinder, M.; Cadelina, G.; Bradley, J.; Rousseau, E.; Willard, R.; Pizzano, J.; Crews, C.; Crew, A.; Taylor, I.; Houston, J. Abstract P5-04-18: ARV-471, an oral estrogen receptor PROTAC degrader for breast cancer. Cancer Res. 2019, 79(Suppl-4), P5-04-18-P05-04-18..
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.
[] [PMID: 30990042]
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.
[] [PMID: 26075522]
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.e417.
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.
[] [PMID: 31792461]
Sun, Y.; Zhao, X.; Ding, N.; Gao, H.; Wu, Y.; Yang, Y.; Zhao, M.; Hwang, J.; Song, Y.; Liu, W.; Rao, 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.
[] [PMID: 29875397]
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.
[] [PMID: 29251720]
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.
[] [PMID: 30802347]
Brand, M.; Jiang, B.; Bauer, S.; Donovan, K.A.; Liang, Y.; Wang, E.S.; Nowak, R.P.; Yuan, J.C.; Zhang, T.; Kwiatkowski, N.; Muller, A.C.; Fischer, E.S.; Gray, N.S.; Winter, G.E. Homolog-selective degradation as a strategy to probe the function of CDK6 in AML. Cell Chem. Biol., 2019, 26(2), 300-306.e309.
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.
[] [PMID: 31330105]
Li, Y.; Yang, J.; Aguilar, A.; McEachern, D.; Przybranowski, S.; Liu, L.; Yang, C.Y.; Wang, M.; Han, X.; Wang, S. Discovery of MD-224 as a first-in-class, highly potent, and efficacious proteolysis targeting chimera murine double minute 2 degrader capable of achieving complete and durable tumor regression. J. Med. Chem., 2019, 62(2), 448-466.
[] [PMID: 30525597]
Wei, J.; Hu, J.; Wang, L.; Xie, L.; Jin, M.S.; Chen, X.; Liu, J.; Jin, J. Discovery of a first-in-class mitogen-activated protein kinase kinase 1/2 (MEK1/2) degrader. J. Med. Chem., 2019, 62(23), 10897-10911.
Song, Y.; Park, P.M.C.; Wu, L.; Ray, A.; Picaud, S.; Li, D.; Wimalasena, V.K.; Du, T.; Filippakopoulos, P.; Anderson, K.C.; Qi, J.; Chauhan, D. Development and preclinical validation of a novel covalent ubiquitin receptor Rpn13 degrader in multiple myeloma. Leukemia, 2019, 33(11), 2685-2694.
[] [PMID: 30962579]
Farnaby, W.; Koegl, M.; Roy, M.J.; Whitworth, C.; Diers, E.; Trainor, N.; Zollman, D.; Steurer, S.; Karolyi-Oezguer, J.; Riedmueller, C.; Gmaschitz, T.; Wachter, J.; Dank, C.; Galant, M.; Sharps, B.; Rumpel, K.; Traxler, E.; Gerstberger, T.; Schnitzer, R.; Petermann, O.; Greb, P.; Weinstabl, H.; Bader, G.; Zoephel, A.; Weiss-Puxbaum, A.; Ehrenhöfer-Wölfer, K.; Wöhrle, S.; Boehmelt, G.; Rinnenthal, J.; Arnhof, H.; Wiechens, N.; Wu, M.Y.; Owen-Hughes, T.; Ettmayer, P.; Pearson, M.; McConnell, D.B.; Ciulli, A. BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design. Nat. Chem. Biol., 2019, 15(7), 672-680.
[] [PMID: 31178587]
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 PROTAC-mediated targeted protein degradation. Cancer Res., 2019, 79(18), 4744-4753.
[] [PMID: 31311809]
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.
[] [PMID: 30427680]
Li, Z.; Pinch, B.J.; Olson, C.M.; Donovan, K.A.; Nowak, R.P.; Mills, C.E.; Scott, D.A.; Doctor, Z.M.; Eleuteri, N.A.; Chung, M.; Sorger, P.K.; Fischer, E.S.; Gray, N.S. Development and characterization of a wee1 kinase degrader. Cell Chem. Biol., 2020, 27(1), 57-65.
[] [PMID: 31735695]
Wardell, S.E.; Yllanes, A.P.; Chao, C.A.; Bae, Y.; Andreano, K.J.; Desautels, T.K.; Heetderks, K.A.; Blitzer, J.T.; Norris, J.D.; McDonnell, D.P. Pharmacokinetic and pharmacodynamic analysis of fulvestrant in preclinical models of breast cancer to assess the importance of its estrogen receptor-alpha degrader activity in antitumor efficacy. Breast Cancer Res. Treat., 2020, 179(1), 67-77.
[] [PMID: 31562570]
Dauvois, S.; Danielian, P.S.; White, R.; Parker, M.G. Antiestrogen ICI 164,384 reduces cellular estrogen receptor content by increasing its turnover. Proc. Natl. Acad. Sci. USA, 1992, 89(9), 4037-4041.
[] [PMID: 1570330]
Thompson, E.W.; Katz, D.; Shima, T.B.; Wakeling, A.E.; Lippman, M.E.; Dickson, R.B. ICI 164,384, a pure antagonist of estrogen-stimulated MCF-7 cell proliferation and invasiveness. Cancer Res., 1989, 49(24 Pt 1), 6929-6934.
[PMID: 2582435]
Gottardis, M.M.; Jiang, S.Y.; Jeng, M.H.; Jordan, V.C. Inhibition of tamoxifen-stimulated growth of an MCF-7 tumor variant in athymic mice by novel steroidal antiestrogens. Cancer Res., 1989, 49(15), 4090-4093.
[PMID: 2743303]
Guo, S.; Zhang, C.; Bratton, M.; Mottamal, M.; Liu, J.; Ma, P.; Zheng, S.; Zhong, Q.; Yang, L.; Wiese, T.E.; Wu, Y.; Ellis, M.J.; Matossian, M.; Burow, M.E.; Miele, L.; Houtman, R.; Wang, G. ZB716, a Steroidal Selective Estrogen Receptor Degrader (SERD), is orally efficacious in blocking tumor growth in mouse xenograft models. Oncotarget, 2018, 9(6), 6924-6937.
[] [PMID: 29467940]
Fan, M.; Rickert, E.L.; Chen, L.; Aftab, S.A.; Nephew, K.P.; Weatherman, R.V. Characterization of molecular and structural determinants of selective estrogen receptor downregulators. Breast Cancer Res. Treat., 2007, 103(1), 37-44.
[] [PMID: 17033922]
Bentrem, D.; Dardes, R.; Liu, H.; MacGregor-Schafer, J.; Zapf, J.; Jordan, V. Molecular mechanism of action at estrogen receptor alpha of a new clinically relevant antiestrogen (GW7604) related to tamoxifen. Endocrinology, 2001, 142(2), 838-846.
[] [PMID: 11159857]
Govek, S.P.; Bonnefous, C.; Julien, J.D.; Nagasawa, J.Y.; Kahraman, M.; Lai, A.G.; Douglas, K.L.; Aparicio, A.M.; Darimont, B.D.; Grillot, K.L.; Joseph, J.D.; Kaufman, J.A.; Lee, K.J.; Lu, N.; Moon, M.J.; Prudente, R.Y.; Sensintaffar, J.; Rix, P.J.; Hager, J.H.; Smith, N.D. Selective estrogen receptor degraders with novel structural motifs induce regression in a tamoxifen-resistant breast cancer xenograft. Bioorg. Med. Chem. Lett., 2019, 29(3), 367-372.
[] [PMID: 30587451]
Lai, A.; Kahraman, M.; Govek, S.; Nagasawa, J.; Bonnefous, C.; Julien, J.; Douglas, K.; Sensintaffar, J.; Lu, N.; Lee, K.J.; Aparicio, A.; Kaufman, J.; Qian, J.; Shao, G.; Prudente, R.; Moon, M.J.; Joseph, J.D.; Darimont, B.; Brigham, D.; Grillot, K.; Heyman, R.; Rix, P.J.; Hager, J.H.; Smith, N.D. Identification of GDC-0810 (ARN-810), an orally bioavailable Selective Estrogen Receptor Degrader (SERD) that demonstrates robust activity in tamoxifen-resistant breast cancer xenografts. J. Med. Chem., 2015, 58(12), 4888-4904.
[] [PMID: 25879485]
Joseph, J.D.; Darimont, B.; Zhou, W.; Arrazate, A.; Young, A.; Ingalla, E.; Walter, K.; Blake, R.A.; Nonomiya, J.; Guan, Z.; Kategaya, L.; Govek, S.P.; Lai, A.G.; Kahraman, M.; Brigham, D.; Sensintaffar, J.; Lu, N.; Shao, G.; Qian, J.; Grillot, K.; Moon, M.; Prudente, R.; Bischoff, E.; Lee, K.J.; Bonnefous, C.; Douglas, K.L.; Julien, J.D.; Nagasawa, J.Y.; Aparicio, A.; Kaufman, J.; Haley, B.; Giltnane, J.M.; Wertz, I.E.; Lackner, M.R.; Nannini, M.A.; Sampath, D.; Schwarz, L.; Manning, H.C.; Tantawy, M.N.; Arteaga, C.L.; Heyman, R.A.; Rix, P.J.; Friedman, L.; Smith, N.D.; Metcalfe, C.; Hager, J.H. The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer. eLife, 2016, 5, 5.
[] [PMID: 27410477]
Cheung, K.W.K.; Yoshida, K.; Cheeti, S.; Chen, B.; Morley, R.; Chan, I.T.; Sahasranaman, S.; Liu, L. GDC-0810 pharmacokinetics and transporter-mediated drug interaction evaluation with an endogenous biomarker in the first-in-human, dose escalation study. Drug Metab. Dispos., 2019, 47(9), 966-973.
[] [PMID: 31266752]
Wang, Y.; Ayres, K.L.; Goldman, D.A.; Dickler, M.N.; Bardia, A.; Mayer, I.A.; Winer, E.; Fredrickson, J.; Arteaga, C.L.; Baselga, J.; Manning, H.C.; Mahmood, U.; Ulaner, G.A. (18)F-Fluoroestradiol PET/CT measurement of estrogen receptor suppression during a phase I trial of the novel estrogen receptor-targeted therapeutic GDC-0810: using an imaging biomarker to guide drug dosage in subsequent trials. Clin. Cancer Res., 2017, 23(12), 3053-3060.
Nardone, A.; Weir, H.; Delpuech, O.; Brown, H.; De Angelis, C.; Cataldo, M.L.; Fu, X.; Shea, M.J.; Mitchell, T.; Veeraraghavan, J.; Nagi, C.; Pilling, M.; Rimawi, M.F.; Trivedi, M.; Hilsenbeck, S.G.; Chamness, G.C.; Jeselsohn, R.; Osborne, C.K.; Schiff, R. The oral selective oestrogen receptor degrader (SERD) AZD9496 is comparable to fulvestrant in antagonising ER and circumventing endocrine resistance. Br. J. Cancer, 2019, 120(3), 331-339.
[] [PMID: 30555156]
Hamilton, E.P.; Patel, M.R.; Armstrong, A.C.; Baird, R.D.; Jhaveri, K.; Hoch, M.; Klinowska, T.; Lindemann, J.P.O.; Morgan, S.R.; Schiavon, G.; Weir, H.M. Im, S.A., A first-in-human study of the new oral selective estrogen receptor degrader AZD9496 for ER(+)/HER2(-) advanced breast cancer. Clin. Cancer Res., 2018, 24, 3510-3518.
Bapiro, T.E.; Sykes, A.; Martin, S.; Davies, M.; Yates, J.W.T.; Hoch, M.; Rollison, H.E.; Jones, B. Complete substrate inhibition of cytochrome P450 2C8 by AZD9496, an oral selective estrogen receptor degrader. Drug Metab. Dispos., 2018, 46(9), 1268-1276.
[] [PMID: 29921707]
Weir, H.M.; Bradbury, R.H.; Lawson, M.; Rabow, A.A.; Buttar, D.; Callis, R.J.; Curwen, J.O.; de Almeida, C.; Ballard, P.; Hulse, M.; Donald, C.S.; Feron, L.J.; Karoutchi, G.; MacFaul, P.; Moss, T.; Norman, R.A.; Pearson, S.E.; Tonge, M.; Davies, G.; Walker, G.E.; Wilson, Z.; Rowlinson, R.; Powell, S.; Sadler, C.; Richmond, G.; Ladd, B.; Pazolli, E.; Mazzola, A.M.; D’Cruz, C.; De Savi, C. AZD9496: An oral estrogen receptor inhibitor that blocks the growth of ER-positive and ESR1-mutant breast tumors in preclinical models. Cancer Res., 2016, 76(11), 3307-3318.
[] [PMID: 27020862]
Garner, F.; Shomali, M.; Paquin, D.; Lyttle, C.R.; Hattersley, G. RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models. Anticancer Drugs, 2015, 26(9), 948-956.
[] [PMID: 26164151]
Wardell, S.E.; Nelson, E.R.; Chao, C.A.; Alley, H.M.; McDonnell, D.P. Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader. Endocr. Relat. Cancer, 2015, 22(5), 713-724.
[] [PMID: 26162914]
Bihani, T.; Patel, H.K.; Arlt, H.; Tao, N.; Jiang, H.; Brown, J.L.; Purandare, D.M.; Hattersley, G.; Garner, F. Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), has antitumor activity in multiple ER(+) breast cancer patient-derived xenograft models. Clin. Cancer Res., 2017, 23(16), 4793-4804.
Bardia, A.; Aftimos, P.; Bihani, T.; Anderson-Villaluz, A.T.; Jung, J.; Conlan, M.G.; Kaklamani, V.G. EMERALD: Phase III trial of elacestrant (RAD1901) vs. endocrine therapy for previously treated ER+ advanced breast cancer. Future Oncol., 2019, 15(28), 3209-3218.
[] [PMID: 31426673]
Tria, G.S.; Abrams, T.; Baird, J.; Burks, H.E.; Firestone, B.; Gaither, L.A.; Hamann, L.G.; He, G.; Kirby, C.A.; Kim, S.; Lombardo, F.; Macchi, K.J.; McDonnell, D.P.; Mishina, Y.; Norris, J.D.; Nunez, J.; Springer, C.; Sun, Y.; Thomsen, N.M.; Wang, C.; Wang, J.; Yu, B.; Tiong-Yip, C.L.; Peukert, S. Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the treatment of estrogen receptor positive breast cancer. J. Med. Chem., 2018, 61(7), 2837-2864.
[] [PMID: 29562737]
Jhaveri, K.; Curigliano, G.; Yap, Y.-S.; Cresta, S.; Duhoux, F.; Terret, C.; Takahashi, S.; Ulaner, G.; Kundamal, N.; Baldoni, D.; Liao, S.; Crystal, A.; Juric, D. Abstract PD1-08: Phase 1/1b study of novel oral selective estrogen receptor degrader (SERD) LSZ102 for estrogen receptor-positive (ER+) advanced breast cancer (ABC) with progression on endocrine therapy (ET). Cancer Res., 2019, 79(Suppl-4), PD1-08-PD01-08..
Juric, D.; Curigliano, G.; Cresta, S.; Yap, Y.-S.; Terret, C.; Duhoux, F.; Takahashi, S.; Kundamal, N.; Bhansali, S.; Liao, S.; Crystal, A.; Jhaveri, K. Abstract P5-21-04: Phase I/Ib study of the SERD LSZ102 alone or in combination with ribociclib in ER+ breast cancer. Cancer Res. 2018, 78(Suppl-4), P5-21-04-P25-21- 04..
Fanning, S.W.; Jeselsohn, R.; Dharmarajan, V.; Mayne, C.G.; Karimi, M.; Buchwalter, G.; Houtman, R.; Toy, W.; Fowler, C.E.; Han, R.; Lainé, M.; Carlson, K.E.; Martin, T.A.; Nowak, J.; Nwachukwu, J.C.; Hosfield, D.J.; Chandarlapaty, S.; Tajkhorshid, E.; Nettles, K.W.; Griffin, P.R.; Shen, Y.; Katzenellenbogen, J.A.; Brown, M.; Greene, G.L. The SERM/SERD bazedoxifene disrupts ESR1 helix 12 to overcome acquired hormone resistance in breast cancer cells. eLife, 2018, 7, 7.
[] [PMID: 30489256]
Loddick, S.A.; Ross, S.J.; Thomason, A.G.; Robinson, D.M.; Walker, G.E.; Dunkley, T.P.; Brave, S.R.; Broadbent, N.; Stratton, N.C.; Trueman, D.; Mouchet, E.; Shaheen, F.S.; Jacobs, V.N.; Cumberbatch, M.; Wilson, J.; Jones, R.D.; Bradbury, R.H.; Rabow, A.; Gaughan, L.; Womack, C.; Barry, S.T.; Robson, C.N.; Critchlow, S.E.; Wedge, S.R.; Brooks, A.N. AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. Mol. Cancer Ther., 2013, 12(9), 1715-1727.
[] [PMID: 23861347]
Omlin, A.; Jones, R.J.; van der Noll, R.; Satoh, T.; Niwakawa, M.; Smith, S.A.; Graham, J.; Ong, M.; Finkelman, R.D.; Schellens, J.H.; Zivi, A.; Crespo, M.; Riisnaes, R.; Nava-Rodrigues, D.; Malone, M.D.; Dive, C.; Sloane, R.; Moore, D.; Alumkal, J.J.; Dymond, A.; Dickinson, P.A.; Ranson, M.; Clack, G.; de Bono, J.; Elliott, T. AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - results of two parallel first-in-human phase I studies. Invest. New Drugs, 2015, 33(3), 679-690.
[] [PMID: 25920479]
Min, A.; Jang, H.; Kim, S.; Lee, K.H.; Kim, D.K.; Suh, K.J.; Yang, Y.; Elvin, P.; O’Connor, M.J. Im, S.A. androgen receptor inhibitor enhances the antitumor effect of PARP inhibitor in breast cancer cells by modulating DNA damage response. Mol. Cancer Ther., 2018, 17(12), 2507-2518.
[] [PMID: 30232143]
Ponnusamy, S.; He, Y.; Hwang, D.J.; Thiyagarajan, T.; Houtman, R.; Bocharova, V.; Sumpter, B.G.; Fernandez, E.; Johnson, D.; Du, Z.; Pfeffer, L.M.; Getzenberg, R.H.; McEwan, I.J.; Miller, D.D.; Narayanan, R. Orally bioavailable androgen receptor degrader, potential next-generation therapeutic for enzalutamide-resistant prostate cancer. Clin. Cancer Res., 2019.
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.
[] [PMID: 26083457]
Xie, T.; Lim, S.M.; Westover, K.D.; Dodge, M.E.; Ercan, D.; Ficarro, S.B.; Udayakumar, D.; Gurbani, D.; Tae, H.S.; Riddle, S.M.; Sim, T.; Marto, J.A.; Jänne, P.A.; Crews, C.M.; Gray, N.S. Pharmacological targeting of the pseudokinase Her3. Nat. Chem. Biol., 2014, 10(12), 1006-1012.
[] [PMID: 25326665]
Ma, A.; Stratikopoulos, E.; Park, K.S.; Wei, J.; Martin, T.C.; Yang, X.; Schwarz, M.; Leshchenko, V.; Rialdi, A.; Dale, B.; Lagana, A.; Guccione, E.; Parekh, S.; Parsons, R.; Jin, J. Discovery of a first-in-class EZH2 selective degrader. Nat. Chem. Biol., 2020, 16, 214-222.
[PMID: 31819273]
Takahashi, D.; Moriyama, J.; Nakamura, T.; Miki, E.; Takahashi, E.; Sato, A.; Akaike, T.; Itto-Nakama, K.; Arimoto, H. AUTACs: Cargo-specific degraders using selective autophagy. Mol. Cell, 2019, 76(5), 797-810.e10.
[] [PMID: 31606272]
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.
[] [PMID: 31263767]
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.
[] [PMID: 28058282]
Bartlett, J.B.; Dredge, K.; Dalgleish, A.G. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat. Rev. Cancer, 2004, 4(4), 314-322.
[] [PMID: 15057291]
Raje, N.; Anderson, K. Thalidomide--a revival story. N. Engl. J. Med., 1999, 341(21), 1606-1609.
[] [PMID: 10564693]
Ito, T.; Ando, H.; Suzuki, T.; Ogura, T.; Hotta, K.; Imamura, Y.; Yamaguchi, Y.; Handa, H. Identification of a primary target of thalidomide teratogenicity. Science, 2010, 327(5971), 1345-1350.
[] [PMID: 20223979]
Donovan, K.A.; An, J.; Nowak, R.P.; Yuan, J.C.; Fink, E.C.; Berry, B.C.; Ebert, B.L.; Fischer, E.S. Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. eLife, 2018, 7, 7.
[] [PMID: 30067223]
Matyskiela, M.E.; Couto, S.; Zheng, X.; Lu, G.; Hui, J.; Stamp, K.; Drew, C.; Ren, Y.; Wang, M.; Carpenter, A.; Lee, C.W.; Clayton, T.; Fang, W.; Lu, C.C.; Riley, M.; Abdubek, P.; Blease, K.; Hartke, J.; Kumar, G.; Vessey, R.; Rolfe, M.; Hamann, L.G.; Chamberlain, P.P. SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate. Nat. Chem. Biol., 2018, 14(10), 981-987.
[] [PMID: 30190590]
Gandhi, A.K.; Kang, J.; Havens, C.G.; Conklin, T.; Ning, Y.; Wu, L.; Ito, T.; Ando, H.; Waldman, M.F.; Thakurta, A.; Klippel, A.; Handa, H.; Daniel, T.O.; Schafer, P.H.; Chopra, R. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). Br. J. Haematol., 2014, 164(6), 811-821.
[] [PMID: 24328678]
Rebollo, A.; Schmitt, C. Ikaros, Aiolos and Helios: transcription regulators and lymphoid malignancies. Immunol. Cell Biol., 2003, 81(3), 171-175.
[] [PMID: 12752680]
Kumar, S.K.; Rajkumar, V.; Kyle, R.A.; van Duin, M.; Sonneveld, P.; Mateos, M.V.; Gay, F.; Anderson, K.C. Multiple myeloma. Nat. Rev. Dis. Primers, 2017, 3, 17046.
[] [PMID: 28726797]
Pan, B.; Lentzsch, S. The application and biology of immunomodulatory drugs (IMiDs) in cancer. Pharmacol. Ther., 2012, 136(1), 56-68.
[] [PMID: 22796518]
Neklesa, T.K.; Winkler, J.D.; Crews, C.M. Targeted protein degradation by PROTACs. Pharmacol. Ther., 2017, 174, 138-144.
[] [PMID: 28223226]
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.
[] [PMID: 11438690]
Lee, H.; Puppala, D.; Choi, E.Y.; Swanson, H.; Kim, K.B. Targeted degradation of the aryl hydrocarbon receptor by the PROTAC approach: a useful chemical genetic tool. ChemBioChem, 2007, 8(17), 2058-2062.
[] [PMID: 17907127]
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.
[] [PMID: 18794799]
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.
[] [PMID: 18752944]
Filippakopoulos, P.; Knapp, S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov., 2014, 13(5), 337-356.
[] [PMID: 24751816]
Belkina, A.C.; Denis, G.V. BET domain co-regulators in obesity, inflammation and cancer. Nat. Rev. Cancer, 2012, 12(7), 465-477.
[] [PMID: 22722403]
Stathis, A.; Bertoni, F. BET proteins as targets for anticancer treatment. Cancer Discov., 2018, 8(1), 24-36.
[] [PMID: 29263030]
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.
[] [PMID: 31200858]
Donati, B.; Lorenzini, E.; Ciarrocchi, A. BRD4 and Cancer: going beyond transcriptional regulation. Mol. Cancer, 2018, 17(1), 164.
[] [PMID: 30466442]
Spradlin, J.N.; Hu, X.; Ward, C.C.; Brittain, S.M.; Jones, M.D.; Ou, L.; To, M.; Proudfoot, A.; Ornelas, E.; Woldegiorgis, M.; Olzmann, J.A.; Bussiere, D.E.; Thomas, J.R.; Tallarico, J.A.; McKenna, J.M.; Schirle, M.; Maimone, T.J.; Nomura, D.K. Harnessing the anti-cancer natural product nimbolide for targeted protein degradation. Nat. Chem. Biol., 2019, 15(7), 747-755.
[] [PMID: 31209351]
Zhang, L.; Riley-Gillis, B.; Vijay, P.; Shen, Y. Acquired Resistance to BET-PROTACs (Proteolysis-Targeting Chimeras) caused by genomic alterations in core components of E3 ligase complexes. Mol. Cancer Ther., 2019, 18(7), 1302-1311.
[] [PMID: 31064868]
Asghar, U.; Witkiewicz, A.K.; Turner, N.C.; Knudsen, E.S. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat. Rev. Drug Discov., 2015, 14(2), 130-146.
[] [PMID: 25633797]
Naito, M.; Ohoka, N.; Shibata, N. SNIPERs-Hijacking IAP activity to induce protein degradation. Drug Discov. Today. Technol., 2019, 31, 35-42.
[] [PMID: 31200857]
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.
[] [PMID: 28154167]
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.
[] [PMID: 29545311]
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.
[] [PMID: 28594553]
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.
[] [PMID: 30202081]
Okuhira, K.; Shoda, T.; Omura, R.; Ohoka, N.; Hattori, T.; Shibata, N.; Demizu, Y.; Sugihara, R.; Ichino, A.; Kawahara, H.; Itoh, Y.; Ishikawa, M.; Hashimoto, Y.; Kurihara, M.; Itoh, S.; Saito, H.; Naito, M. Targeted degradation of proteins localized in subcellular compartments by hybrid small molecules. Mol. Pharmacol., 2017, 91(3), 159-166.
[] [PMID: 27965304]
Yerbury, J.J.; Stewart, E.M.; Wyatt, A.R.; Wilson, M.R. Quality control of protein folding in extracellular space. EMBO Rep., 2005, 6(12), 1131-1136.
[] [PMID: 16319958]
Wu, Y.L.; Yang, X.; Ren, Z.; McDonnell, D.P.; Norris, J.D.; Willson, T.M.; Greene, G.L. Structural basis for an unexpected mode of SERM-mediated ER antagonism. Mol. Cell, 2005, 18(4), 413-424.
[] [PMID: 15893725]
Wittmann, B.M.; Sherk, A.; McDonnell, D.P. Definition of functionally important mechanistic differences among selective estrogen receptor down-regulators. Cancer Res., 2007, 67(19), 9549-9560.
[] [PMID: 17909066]
Soleja, M.; Raj, G.V.; Unni, N. An evaluation of fulvestrant for the treatment of metastatic breast cancer. Expert Opin. Pharmacother., 2019, 20(15), 1819-1829.
[] [PMID: 31486688]
Patel, H.K.; Bihani, T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment. Pharmacol. Ther., 2018, 186, 1-24.
[] [PMID: 29289555]
Neklesa, T.K.; Tae, H.S.; Schneekloth, A.R.; Stulberg, M.J.; Corson, T.W.; Sundberg, T.B.; Raina, K.; Holley, S.A.; Crews, C.M. Small-molecule hydrophobic tagging-induced degradation of HaloTag fusion proteins. Nat. Chem. Biol., 2011, 7(8), 538-543.
[] [PMID: 21725302]
Lim, S.M.; Xie, T.; Westover, K.D.; Ficarro, S.B.; Tae, H.S.; Gurbani, D.; Sim, T.; Marto, J.A.; Jänne, P.A.; Crews, C.M.; Gray, N.S. Development of small molecules targeting the pseudokinase Her3. Bioorg. Med. Chem. Lett., 2015, 25(16), 3382-3389.
[] [PMID: 26094118]

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