Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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

Advances in the Design and Development of PROTAC-mediated HDAC Degradation

Author(s): Daniel Alencar Rodrigues*, Andrew Roe, Darren Griffith and Tríona Ní Chonghaile

Volume 22, Issue 5, 2022

Published on: 29 November, 2021

Page: [408 - 424] Pages: 17

DOI: 10.2174/1568026621666211015092047

Price: $65

Abstract

Due to developments in modern chemistry, previously uundruggable substrates are now targetable thanks to selective degradation using the ubiquitin-proteasomal degradation system. PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules designed specifically to degrade target proteins. They are of significant interest to industry and academia as they are highly specific and can target previously undruggable target proteins from transcription factors to enzymes. More than 15 degraders are expected to be evaluated in clinical trials by the end of 2021. Herein, we describe recent advances in the design and development of PROTAC-mediated degradation of histone deacetylases (HDACs). PROTAC-mediated degradation of HDACs can offer some significant advantages over direct inhibition, such as the use of substoichiometric doses and the potential to disrupt enzyme-independent HDAC function. We discuss the potential implication of the degradation of HDACs in comparison with HDAC knockout studies. Along with the selection of HDAC inhibitors and E3 ligase ligands for the design of PROTACs. The potential utility of HDAC PROTACs in various disease pathologies from cancer to inflammation to neurodegeneration is driving the interest in this field.

Keywords: PROTACs, HDAC, HDAC inhibitors, HDAC degraders, multitarget, IAP.

« Previous
Graphical Abstract

[1]
Toure, M.; Crews, C.M. Small-molecule PROTACS: new approaches to protein degradation. Angew. Chem. Int. Ed. Engl., 2016, 55(6), 1966-1973.
[http://dx.doi.org/10.1002/anie.201507978] [PMID: 26756721]
[2]
Sun, X.; Gao, H.; Yang, Y.; He, M.; Wu, Y.; Song, Y.; Tong, Y.; Rao, Y. PROTACs: great opportunities for academia and industry. Signal Transduct. Target. Ther., 2019, 4(1), 64.
[http://dx.doi.org/10.1038/s41392-019-0101-6] [PMID: 31885879]
[3]
An, S.; Fu, L. Small-molecule PROTACs: an emerging and promising approach for the development of targeted therapy drugs. EBioMedicine, 2018, 36, 553-562.
[http://dx.doi.org/10.1016/j.ebiom.2018.09.005] [PMID: 30224312]
[4]
Li, X.; Song, Y. Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy. J. Hematol. Oncol., 2020, 13(1), 50.
[http://dx.doi.org/10.1186/s13045-020-00885-3] [PMID: 32404196]
[5]
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]
[6]
Chamberlain, P.P.; Hamann, L.G. Development of targeted protein degradation therapeutics. Nat. Chem. Biol., 2019, 15(10), 937-944.
[http://dx.doi.org/10.1038/s41589-019-0362-y] [PMID: 31527835]
[7]
Schapira, M.; Calabrese, M.F.; Bullock, A.N.; Crews, C.M. Targeted protein degradation: expanding the toolbox. Nat. Rev. Drug Discov., 2019, 18(12), 949-963.
[http://dx.doi.org/10.1038/s41573-019-0047-y] [PMID: 31666732]
[8]
Pettersson, M.; Crews, C.M. PROteolysis TArgeting Chimeras (PROTACs) - past, present and future. Drug Discov. Today. Technol., 2019, 31, 15-27.
[http://dx.doi.org/10.1016/j.ddtec.2019.01.002] [PMID: 31200855]
[9]
Burslem, G.M.; Crews, C.M. Small-molecule modulation of protein homeostasis. Chem. Rev., 2017, 117(17), 11269-11301.
[http://dx.doi.org/10.1021/acs.chemrev.7b00077] [PMID: 28777566]
[10]
Girardini, M.; Maniaci, C.; Hughes, S.J.; Testa, A.; Ciulli, A. Cereblon versus VHL: Hijacking E3 ligases against each other using PROTACs. Bioorg. Med. Chem., 2019, 27(12), 2466-2479.
[http://dx.doi.org/10.1016/j.bmc.2019.02.048] [PMID: 30826187]
[11]
Mullard, A. Targeted protein degraders crowd into the clinic. Nat. Rev. Drug Discov., 2021, 20(4), 247-250.
[http://dx.doi.org/10.1038/d41573-021-00052-4] [PMID: 33737725]
[12]
Schreiber, S.L. The rise of molecular glues. Cell, 2021, 184(1), 3-9.
[http://dx.doi.org/10.1016/j.cell.2020.12.020] [PMID: 33417864]
[13]
Drazic, A.; Myklebust, L.M.; Ree, R.; Arnesen, T. The world of protein acetylation. Biochim. Biophys. Acta, 2016, 1864(10), 1372-1401.
[http://dx.doi.org/10.1016/j.bbapap.2016.06.007] [PMID: 27296530]
[14]
Christensen, D.G.; Xie, X.; Basisty, N.; Byrnes, J.; McSweeney, S.; Schilling, B.; Wolfe, A.J. Post-translational protein acetylation: an elegant mechanism for bacteria to dynamically regulate metabolic functions. Front. Microbiol., 2019, 10, 1604.
[http://dx.doi.org/10.3389/fmicb.2019.01604] [PMID: 31354686]
[15]
Albaugh, B.N.; Arnold, K.M.; Denu, J.M. KAT(ching) metabolism by the tail: insight into the links between lysine acetyltransferases and metabolism. ChemBioChem, 2011, 12(2), 290-298.
[http://dx.doi.org/10.1002/cbic.201000438] [PMID: 21243716]
[16]
Kouzarides, T. Chromatin modifications and their function. Cell, 2007, 128(4), 693-705.
[http://dx.doi.org/10.1016/j.cell.2007.02.005] [PMID: 17320507]
[17]
Glozak, M.A.; Seto, E. Histone deacetylases and cancer. Oncogene, 2007, 26(37), 5420-5432.
[http://dx.doi.org/10.1038/sj.onc.1210610] [PMID: 17694083]
[18]
Witt, O.; Deubzer, H.E.; Milde, T.; Oehme, I. HDAC family: what are the cancer relevant targets? Cancer Lett., 2009, 277(1), 8-21.
[http://dx.doi.org/10.1016/j.canlet.2008.08.016] [PMID: 18824292]
[19]
Dokmanovic, M.; Clarke, C.; Marks, P.A. Histone deacetylase inhibitors: overview and perspectives. Mol. Cancer Res., 2007, 5(10), 981-989.
[http://dx.doi.org/10.1158/1541-7786.MCR-07-0324] [PMID: 17951399]
[20]
Falkenberg, K.J.; Johnstone, R.W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat. Rev. Drug Discov., 2014, 13(9), 673-691.
[http://dx.doi.org/10.1038/nrd4360] [PMID: 25131830]
[21]
Bolden, J.E.; Peart, M.J.; Johnstone, R.W. Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov., 2006, 5(9), 769-784.
[http://dx.doi.org/10.1038/nrd2133] [PMID: 16955068]
[22]
Liu, T.; Kuljaca, S.; Tee, A.; Marshall, G.M. Histone deacetylase inhibitors: multifunctional anticancer agents. Cancer Treat. Rev., 2006, 32(3), 157-165.
[http://dx.doi.org/10.1016/j.ctrv.2005.12.006] [PMID: 16516391]
[23]
Yoshida, M.; Kudo, N.; Kosono, S.; Ito, A. Chemical and structural biology of protein lysine deacetylases. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 2017, 93(5), 297-321.
[http://dx.doi.org/10.2183/pjab.93.019] [PMID: 28496053]
[24]
Morel, D.; Jeffery, D.; Aspeslagh, S.; Almouzni, G.; Postel-Vinay, S. Combining epigenetic drugs with other therapies for solid tumours - past lessons and future promise. Nat. Rev. Clin. Oncol., 2020, 17(2), 91-107.
[http://dx.doi.org/10.1038/s41571-019-0267-4] [PMID: 31570827]
[25]
Gregoretti, I.V.; Lee, Y-M.; Goodson, H.V. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J. Mol. Biol., 2004, 338(1), 17-31.
[http://dx.doi.org/10.1016/j.jmb.2004.02.006] [PMID: 15050820]
[26]
Marks, P.A.; Breslow, R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat. Biotechnol., 2007, 25(1), 84-90.
[http://dx.doi.org/10.1038/nbt1272] [PMID: 17211407]
[27]
Yang, L.P. Romidepsin: in the treatment of T-cell lymphoma. Drugs, 2011, 71(11), 1469-1480.
[http://dx.doi.org/10.2165/11207170-000000000-00000] [PMID: 21812508]
[28]
Prince, H.M.; Dickinson, M. Romidepsin for cutaneous T-cell lymphoma. Clin. Cancer Res., 2012, 18(13), 3509-3515.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-3144] [PMID: 22535155]
[29]
Poole, R.M. Belinostat: first global approval. Drugs, 2014, 74(13), 1543-1554.
[http://dx.doi.org/10.1007/s40265-014-0275-8] [PMID: 25134672]
[30]
Garnock-Jones, K.P. Panobinostat: first global approval. Drugs, 2015, 75(6), 695-704.
[http://dx.doi.org/10.1007/s40265-015-0388-8] [PMID: 25837990]
[31]
Zeng, H.; Qu, J.; Jin, N.; Xu, J.; Lin, C.; Chen, Y.; Yang, X.; He, X.; Tang, S.; Lan, X.; Yang, X.; Chen, Z.; Huang, M.; Ding, J.; Geng, M. Feedback activation of leukemia inhibitory factor receptor limits response to histone deacetylase inhibitors in breast cancer. Cancer Cell, 2016, 30(3), 459-473.
[http://dx.doi.org/10.1016/j.ccell.2016.08.001] [PMID: 27622335]
[32]
Thurn, K.T.; Thomas, S.; Moore, A.; Munster, P.N. Rational therapeutic combinations with histone deacetylase inhibitors for the treatment of cancer. Future Oncol., 2011, 7(2), 263-283.
[http://dx.doi.org/10.2217/fon.11.2] [PMID: 21345145]
[33]
Miller, T.A.; Witter, D.J.; Belvedere, S. Histone deacetylase inhibitors. J. Med. Chem., 2003, 46(24), 5097-5116.
[http://dx.doi.org/10.1021/jm0303094] [PMID: 14613312]
[34]
Rodrigues, D.A.; Thota, S.; Fraga, C.A. Beyond the selective inhibition of histone deacetylase 6. Mini Rev. Med. Chem., 2016, 16(14), 1175-1184.
[http://dx.doi.org/10.2174/1389557516666160428115959] [PMID: 27121714]
[35]
Beshore, D.C.; Adam, G.C.; Barnard, R.J.O.; Burlein, C.; Gallicchio, S.N.; Holloway, M.K.; Krosky, D.; Lemaire, W.; Myers, R.W.; Patel, S.; Plotkin, M.A.; Powell, D.A.; Rada, V.; Cox, C.D.; Coleman, P.J.; Klein, D.J.; Wolkenberg, S.E. Redefining the histone deacetylase inhibitor pharmacophore: high potency with no zinc cofactor interaction. ACS Med. Chem. Lett., 2021, 12(4), 540-547.
[http://dx.doi.org/10.1021/acsmedchemlett.1c00074] [PMID: 33854701]
[36]
Ganesan, A. Multitarget drugs: an epigenetic epiphany. ChemMedChem, 2016, 11(12), 1227-1241.
[http://dx.doi.org/10.1002/cmdc.201500394] [PMID: 26891251]
[37]
Hesham, H.M.; Lasheen, D.S.; Abouzid, K.A.M. Chimeric HDAC inhibitors: comprehensive review on the HDAC-based strategies developed to combat cancer. Med. Res. Rev., 2018, 38(6), 2058-2109.
[http://dx.doi.org/10.1002/med.21505] [PMID: 29733427]
[38]
Luan, Y.; Li, J.; Bernatchez, J.A.; Li, R. Kinase and histone deacetylase hybrid inhibitors for cancer therapy. J. Med. Chem., 2019, 62(7), 3171-3183.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00189] [PMID: 30418766]
[39]
Musso, L.; Dallavalle, S.; Zunino, F. Perspectives in the development of hybrid bifunctional antitumour agents. Biochem. Pharmacol., 2015, 96(4), 297-305.
[http://dx.doi.org/10.1016/j.bcp.2015.06.006] [PMID: 26074269]
[40]
Liu, T.; Wan, Y.; Xiao, Y.; Xia, C.; Duan, G. Dual-target inhibitors based on HDACs: novel antitumor agents for cancer therapy. J. Med. Chem., 2020, 63(17), 8977-9002.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00491] [PMID: 32320239]
[41]
de Lera, A.R.; Ganesan, A. Two-hit wonders: The expanding universe of multitargeting epigenetic agents. Curr. Opin. Chem. Biol., 2020, 57, 135-154.
[http://dx.doi.org/10.1016/j.cbpa.2020.05.009] [PMID: 32784072]
[42]
Tomaselli, D.; Lucidi, A.; Rotili, D.; Mai, A. Epigenetic polypharmacology: A new frontier for epi-drug discovery. Med. Res. Rev., 2020, 40(1), 190-244.
[http://dx.doi.org/10.1002/med.21600] [PMID: 31218726]
[43]
Rodrigues, D.A.; Pinheiro, P.S.M.; Fraga, C.A.M. Multitarget Inhibition of Histone Deacetylase (HDAC) and Phosphatidylinositol-3-kinase (PI3K): current and future prospects. ChemMedChem, 2021, 16(3), 448-457.
[http://dx.doi.org/10.1002/cmdc.202000643] [PMID: 33049098]
[44]
Montgomery, R.L.; Hsieh, J.; Barbosa, A.C.; Richardson, J.A.; Olson, E.N. Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development. Proc. Natl. Acad. Sci. USA, 2009, 106(19), 7876-7881.
[http://dx.doi.org/10.1073/pnas.0902750106] [PMID: 19380719]
[45]
Yamaguchi, T.; Cubizolles, F.; Zhang, Y.; Reichert, N.; Kohler, H.; Seiser, C.; Matthias, P. Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progression. Genes Dev., 2010, 24(5), 455-469.
[http://dx.doi.org/10.1101/gad.552310] [PMID: 20194438]
[46]
Bhaskara, S.; Knutson, S.K.; Jiang, G.; Chandrasekharan, M.B.; Wilson, A.J.; Zheng, S.; Yenamandra, A.; Locke, K.; Yuan, J.L.; Bonine-Summers, A.R.; Wells, C.E.; Kaiser, J.F.; Washington, M.K.; Zhao, Z.; Wagner, F.F.; Sun, Z.W.; Xia, F.; Holson, E.B.; Khabele, D.; Hiebert, S.W. Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell, 2010, 18(5), 436-447.
[http://dx.doi.org/10.1016/j.ccr.2010.10.022] [PMID: 21075309]
[47]
Norwood, J.; Franklin, J.M.; Sharma, D.; D’Mello, S.R. Histone deacetylase 3 is necessary for proper brain development. J. Biol. Chem., 2014, 289(50), 34569-34582.
[http://dx.doi.org/10.1074/jbc.M114.576397] [PMID: 25339172]
[48]
Ferrari, A.; Longo, R.; Fiorino, E.; Silva, R.; Mitro, N.; Cermenati, G.; Gilardi, F.; Desvergne, B.; Andolfo, A.; Magagnotti, C.; Caruso, D.; Fabiani, E.; Hiebert, S.W.; Crestani, M. HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning. Nat. Commun., 2017, 8(1), 93.
[http://dx.doi.org/10.1038/s41467-017-00182-7] [PMID: 28733645]
[49]
Katayama, S.; Morii, A.; Makanga, J.O.; Suzuki, T.; Miyata, N.; Inazu, T. HDAC8 regulates neural differentiation through embryoid body formation in P19 cells. Biochem. Biophys. Res. Commun., 2018, 498(1), 45-51.
[http://dx.doi.org/10.1016/j.bbrc.2018.02.195] [PMID: 29499194]
[50]
Paradis, F.H.; Hales, B.F. The effects of class-specific histone deacetylase inhibitors on the development of limbs during organogenesis. Toxicol. Sci., 2015, 148(1), 220-228.
[http://dx.doi.org/10.1093/toxsci/kfv174] [PMID: 26251326]
[51]
Luo, L.; Martin, S.C.; Parkington, J.; Cadena, S.M.; Zhu, J.; Ibebunjo, C.; Summermatter, S.; Londraville, N.; Patora-Komisarska, K.; Widler, L.; Zhai, H.; Trendelenburg, A.U.; Glass, D.J.; Shi, J. HDAC4 controls muscle homeostasis through deacetylation of myosin heavy chain, PGC-1α, and Hsc70. Cell Rep., 2019, 29(3), 749-763.e12.
[http://dx.doi.org/10.1016/j.celrep.2019.09.023] [PMID: 31618641]
[52]
Moresi, V.; Williams, A.H.; Meadows, E.; Flynn, J.M.; Potthoff, M.J.; McAnally, J.; Shelton, J.M.; Backs, J.; Klein, W.H.; Richardson, J.A.; Bassel-Duby, R.; Olson, E.N. Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. Cell, 2010, 143(1), 35-45.
[http://dx.doi.org/10.1016/j.cell.2010.09.004] [PMID: 20887891]
[53]
Haberland, M.; Montgomery, R.L.; Olson, E.N. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat. Rev. Genet., 2009, 10(1), 32-42.
[http://dx.doi.org/10.1038/nrg2485] [PMID: 19065135]
[54]
Agis-Balboa, R.C.; Pavelka, Z.; Kerimoglu, C.; Fischer, A. Loss of HDAC5 impairs memory function: implications for Alzheimer’s disease. J. Alzheimers Dis., 2013, 33(1), 35-44.
[http://dx.doi.org/10.3233/JAD-2012-121009] [PMID: 22914591]
[55]
Kabra, D.G.; Pfuhlmann, K.; García-Cáceres, C.; Schriever, S.C.; Casquero García, V.; Kebede, A.F.; Fuente-Martin, E.; Trivedi, C.; Heppner, K.; Uhlenhaut, N.H.; Legutko, B.; Kabra, U.D.; Gao, Y.; Yi, C.X.; Quarta, C.; Clemmensen, C.; Finan, B.; Müller, T.D.; Meyer, C.W.; Paez-Pereda, M.; Stemmer, K.; Woods, S.C.; Perez-Tilve, D.; Schneider, R.; Olson, E.N.; Tschöp, M.H.; Pfluger, P.T. Hypothalamic leptin action is mediated by histone deacetylase 5. Nat. Commun., 2016, 7, 10782.
[http://dx.doi.org/10.1038/ncomms10782] [PMID: 26923837]
[56]
Kasler, H.G.; Young, B.D.; Mottet, D.; Lim, H.W.; Collins, A.M.; Olson, E.N.; Verdin, E. Histone deacetylase 7 regulates cell survival and TCR signaling in CD4/CD8 double-positive thymocytes. J. Immunol., 2011, 186(8), 4782-4793.
[http://dx.doi.org/10.4049/jimmunol.1001179] [PMID: 21398603]
[57]
Kasler, H.G.; Lim, H.W.; Mottet, D.; Collins, A.M.; Lee, I.S.; Verdin, E. Nuclear export of histone deacetylase 7 during thymic selection is required for immune self-tolerance. EMBO J., 2012, 31(23), 4453-4465.
[http://dx.doi.org/10.1038/emboj.2012.295] [PMID: 23103766]
[58]
Kasler, H.G.; Lee, I.S.; Lim, H.W.; Verdin, E. Histone Deacetylase 7 mediates tissue-specific autoimmunity via control of innate effector function in invariant Natural Killer T Cells. eLife, 2018, 7, e32109.
[http://dx.doi.org/10.7554/eLife.32109] [PMID: 29664401]
[59]
Tao, R.; de Zoeten, E.F.; Ozkaynak, E.; Chen, C.; Wang, L.; Porrett, P.M.; Li, B.; Turka, L.A.; Olson, E.N.; Greene, M.I.; Wells, A.D.; Hancock, W.W. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat. Med., 2007, 13(11), 1299-1307.
[http://dx.doi.org/10.1038/nm1652] [PMID: 17922010]
[60]
de Zoeten, E.F.; Wang, L.; Sai, H.; Dillmann, W.H.; Hancock, W.W. Inhibition of HDAC9 increases T regulatory cell function and prevents colitis in mice. Gastroenterology, 2010, 138(2), 583-594.
[http://dx.doi.org/10.1053/j.gastro.2009.10.037] [PMID: 19879272]
[61]
Yan, K.; Cao, Q.; Reilly, C.M.; Young, N.L.; Garcia, B.A.; Mishra, N. Histone deacetylase 9 deficiency protects against effector T cell-mediated systemic autoimmunity. J. Biol. Chem., 2011, 286(33), 28833-28843.
[http://dx.doi.org/10.1074/jbc.M111.233932] [PMID: 21708950]
[62]
Wang, X.; Waschke, B.C.; Woolaver, R.A.; Chen, S.M.Y.; Chen, Z.; Wang, J.H. HDAC inhibitors overcome immunotherapy resistance in B-cell lymphoma. Protein Cell, 2020, 11(7), 472-482.
[http://dx.doi.org/10.1007/s13238-020-00694-x] [PMID: 32162275]
[63]
Guerriero, J.L.; Sotayo, A.; Ponichtera, H.E.; Castrillon, J.A.; Pourzia, A.L.; Schad, S.; Johnson, S.F.; Carrasco, R.D.; Lazo, S.; Bronson, R.T.; Davis, S.P.; Lobera, M.; Nolan, M.A.; Letai, A. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature, 2017, 543(7645), 428-432.
[http://dx.doi.org/10.1038/nature21409] [PMID: 28273064]
[64]
Li, Y.; Shin, D.; Kwon, S.H. Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes. FEBS J., 2013, 280(3), 775-793.
[PMID: 23181831]
[65]
Dowling, C.M.; Hollinshead, K.E.R.; Di Grande, A.; Pritchard, J.; Zhang, H.; Dillon, E.T.; Haley, K.; Papadopoulos, E.; Mehta, A.K.; Bleach, R.; Lindner, A.U.; Mooney, B.; Düssmann, H.; O’Connor, D.; Prehn, J.H.M.; Wynne, K.; Hemann, M.; Bradner, J.E.; Kimmelman, A.C.; Guerriero, J.L.; Cagney, G.; Wong, K.K.; Letai, A.G.; Chonghaile, T.N. Multiple screening approaches reveal HDAC6 as a novel regulator of glycolytic metabolism in triple-negative breast cancer. Sci. Adv., 2021, 7(3), eabc4897.
[http://dx.doi.org/10.1126/sciadv.abc4897] [PMID: 33523897]
[66]
Gu, S.; Liu, Y.; Zhu, B.; Ding, K.; Yao, T.P.; Chen, F.; Zhan, L.; Xu, P.; Ehrlich, M.; Liang, T.; Lin, X.; Feng, X.H. Loss of α-Tubulin acetylation is associated with TGF-β-induced epithelial-mesenchymal transition. J. Biol. Chem., 2016, 291(10), 5396-5405.
[http://dx.doi.org/10.1074/jbc.M115.713123] [PMID: 26763233]
[67]
Saji, S.; Kawakami, M.; Hayashi, S.; Yoshida, N.; Hirose, M.; Horiguchi, S.; Itoh, A.; Funata, N.; Schreiber, S.L.; Yoshida, M.; Toi, M. Significance of HDAC6 regulation via estrogen signaling for cell motility and prognosis in estrogen receptor-positive breast cancer. Oncogene, 2005, 24(28), 4531-4539.
[http://dx.doi.org/10.1038/sj.onc.1208646] [PMID: 15806142]
[68]
Lee, Y.S.; Lim, K.H.; Guo, X.; Kawaguchi, Y.; Gao, Y.; Barrientos, T.; Ordentlich, P.; Wang, X.F.; Counter, C.M.; Yao, T.P. The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis. Cancer Res., 2008, 68(18), 7561-7569.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0188] [PMID: 18794144]
[69]
Knox, T.; Sahakian, E.; Banik, D.; Hadley, M.; Palmer, E.; Noonepalle, S.; Kim, J.; Powers, J.; Gracia-Hernandez, M.; Oliveira, V.; Cheng, F.; Chen, J.; Barinka, C.; Pinilla-Ibarz, J.; Lee, N.H.; Kozikowski, A.; Villagra, A. Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells. Sci. Rep., 2019, 9(1), 6136.
[http://dx.doi.org/10.1038/s41598-019-42237-3] [PMID: 30992475]
[70]
Govindarajan, N.; Rao, P.; Burkhardt, S.; Sananbenesi, F.; Schlüter, O.M.; Bradke, F.; Lu, J.; Fischer, A. Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer’s disease. EMBO Mol. Med., 2013, 5(1), 52-63.
[http://dx.doi.org/10.1002/emmm.201201923] [PMID: 23184605]
[71]
Li, Y.; Peng, L.; Seto, E. Histone deacetylase 10 regulates the cell cycle G2/M phase transition via a novel let-7-HMGA2-cyclin A2 pathway. Mol. Cell. Biol., 2015, 35(20), 3547-3565.
[http://dx.doi.org/10.1128/MCB.00400-15] [PMID: 26240284]
[72]
Obayashi, H.; Nagano, Y.; Takahashi, T.; Seki, T.; Tanaka, S.; Sakai, N.; Matsumoto, M.; Maruyama, H. Histone deacetylase 10 knockout activates chaperone-mediated autophagy and accelerates the decomposition of its substrate. Biochem. Biophys. Res. Commun., 2020, 523(1), 246-252.
[http://dx.doi.org/10.1016/j.bbrc.2019.12.048] [PMID: 31862140]
[73]
Bagchi, R.A.; Ferguson, B.S.; Stratton, M.S.; Hu, T.; Cavasin, M.A.; Sun, L.; Lin, Y.H.; Liu, D.; Londono, P.; Song, K.; Pino, M.F.; Sparks, L.M.; Smith, S.R.; Scherer, P.E.; Collins, S.; Seto, E.; McKinsey, T.A. HDAC11 suppresses the thermogenic program of adipose tissue via BRD2. JCI Insight, 2018, 3(15), 120159.
[http://dx.doi.org/10.1172/jci.insight.120159] [PMID: 30089714]
[74]
Hurtado, E.; Núñez-Álvarez, Y.; Muñoz, M.; Gutiérrez-Caballero, C.; Casas, J.; Pendás, A.M.; Peinado, M.A.; Suelves, M. HDAC11 is a novel regulator of fatty acid oxidative metabolism in skeletal muscle. FEBS J., 2021, 288(3), 902-919.
[http://dx.doi.org/10.1111/febs.15456] [PMID: 32563202]
[75]
Gao, L.; Cueto, M.A.; Asselbergs, F.; Atadja, P. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J. Biol. Chem., 2002, 277(28), 25748-25755.
[http://dx.doi.org/10.1074/jbc.M111871200] [PMID: 11948178]
[76]
Montgomery, R.L.; Davis, C.A.; Potthoff, M.J.; Haberland, M.; Fielitz, J.; Qi, X.; Hill, J.A.; Richardson, J.A.; Olson, E.N. Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev., 2007, 21(14), 1790-1802.
[http://dx.doi.org/10.1101/gad.1563807] [PMID: 17639084]
[77]
Trivedi, C.M.; Luo, Y.; Yin, Z.; Zhang, M.; Zhu, W.; Wang, T.; Floss, T.; Goettlicher, M.; Noppinger, P.R.; Wurst, W.; Ferrari, V.A.; Abrams, C.S.; Gruber, P.J.; Epstein, J.A. Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Nat. Med., 2007, 13(3), 324-331.
[http://dx.doi.org/10.1038/nm1552] [PMID: 17322895]
[78]
Montgomery, R.L.; Potthoff, M.J.; Haberland, M.; Qi, X.; Matsuzaki, S.; Humphries, K.M.; Richardson, J.A.; Bassel-Duby, R.; Olson, E.N. Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice. J. Clin. Invest., 2008, 118(11), 3588-3597.
[http://dx.doi.org/10.1172/JCI35847] [PMID: 18830415]
[79]
Haberland, M.; Mokalled, M.H.; Montgomery, R.L.; Olson, E.N. Epigenetic control of skull morphogenesis by histone deacetylase 8. Genes Dev., 2009, 23(14), 1625-1630.
[http://dx.doi.org/10.1101/gad.1809209] [PMID: 19605684]
[80]
Vega, R.B.; Matsuda, K.; Oh, J.; Barbosa, A.C.; Yang, X.; Meadows, E.; McAnally, J.; Pomajzl, C.; Shelton, J.M.; Richardson, J.A.; Karsenty, G.; Olson, E.N. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell, 2004, 119(4), 555-566.
[http://dx.doi.org/10.1016/j.cell.2004.10.024] [PMID: 15537544]
[81]
Chang, S.; McKinsey, T.A.; Zhang, C.L.; Richardson, J.A.; Hill, J.A.; Olson, E.N. Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development. Mol. Cell. Biol., 2004, 24(19), 8467-8476.
[http://dx.doi.org/10.1128/MCB.24.19.8467-8476.2004] [PMID: 15367668]
[82]
Chang, S.; Young, B.D.; Li, S.; Qi, X.; Richardson, J.A.; Olson, E.N. Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10. Cell, 2006, 126(2), 321-334.
[http://dx.doi.org/10.1016/j.cell.2006.05.040] [PMID: 16873063]
[83]
Zhang, Y.; Kwon, S.; Yamaguchi, T.; Cubizolles, F.; Rousseaux, S.; Kneissel, M.; Cao, C.; Li, N.; Cheng, H.L.; Chua, K.; Lombard, D.; Mizeracki, A.; Matthias, G.; Alt, F.W.; Khochbin, S.; Matthias, P. Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol. Cell. Biol., 2008, 28(5), 1688-1701.
[http://dx.doi.org/10.1128/MCB.01154-06] [PMID: 18180281]
[84]
Dahiya, S.; Beier, U.H.; Wang, L.; Han, R.; Jiao, J.; Akimova, T.; Angelin, A.; Wallace, D.C.; Hancock, W.W. HDAC10 deletion promotes Foxp3+ T-regulatory cell function. Sci. Rep., 2020, 10(1), 424.
[http://dx.doi.org/10.1038/s41598-019-57294-x] [PMID: 31949209]
[85]
Bryant, D.T.; Landles, C.; Papadopoulou, A.S.; Benjamin, A.C.; Duckworth, J.K.; Rosahl, T.; Benn, C.L.; Bates, G.P. Disruption to schizophrenia-associated gene Fez1 in the hippocampus of HDAC11 knockout mice. Sci. Rep., 2017, 7(1), 11900.
[http://dx.doi.org/10.1038/s41598-017-11630-1] [PMID: 28928414]
[86]
Xiong, Y.; Donovan, K.A.; Eleuteri, N.A.; Kirmani, N.; Yue, H.; Razov, A.; Krupnick, N.M.; Nowak, R.P.; Fischer, E.S. Chemo-proteomics exploration of HDAC degradability by small molecule degraders. Cell Chem. Biol., 2021, S2451-9456(21)00312-3.
[PMID: 34314730]
[87]
Okamoto, T.; Imaizumi, K.; Kaneko, M. The role of tissue-specific ubiquitin ligases, RNF183, RNF186, RNF182 and RNF152, in disease and biological function. Int. J. Mol. Sci., 2020, 21(11), 3921.
[http://dx.doi.org/10.3390/ijms21113921] [PMID: 32486221]
[88]
George, A.J.; Hoffiz, Y.C.; Charles, A.J.; Zhu, Y.; Mabb, A.M. A comprehensive Atlas of E3 ubiquitin ligase mutations in neurological disorders. Front. Genet., 2018, 9, 29.
[http://dx.doi.org/10.3389/fgene.2018.00029] [PMID: 29491882]
[89]
Zheng, N.; Shabek, N. Ubiquitin ligases: structure, function, and regulation. Annu. Rev. Biochem., 2017, 86, 129-157.
[http://dx.doi.org/10.1146/annurev-biochem-060815-014922] [PMID: 28375744]
[90]
Ishida, T.; Ciulli, A. E3 ligase ligands for PROTACs: how they were found and how to discover new ones. SLAS Discov., 2021, 26(4), 484-502.
[http://dx.doi.org/10.1177/2472555220965528] [PMID: 33143537]
[91]
Douglass, E.F., Jr; Miller, C.J.; Sparer, G.; Shapiro, H.; Spiegel, D.A. A comprehensive mathematical model for three-body binding equilibria. J. Am. Chem. Soc., 2013, 135(16), 6092-6099.
[http://dx.doi.org/10.1021/ja311795d] [PMID: 23544844]
[92]
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]
[93]
Yang, K.; Wu, H.; Zhang, Z.; Leisten, E.D.; Nie, X.; Liu, B.; Wen, Z.; Zhang, J.; Cunningham, M.D.; Tang, W. Development of Selective Histone Deacetylase 6 (HDAC6) degraders recruiting Von Hippel-Lindau (VHL) E3 ubiquitin ligase. ACS Med. Chem. Lett., 2020, 11(4), 575-581.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00046] [PMID: 32292566]
[94]
Nabet, B.; Roberts, J.M.; Buckley, D.L.; Paulk, J.; Dastjerdi, S.; Yang, A.; Leggett, A.L.; Erb, M.A.; Lawlor, M.A.; Souza, A.; Scott, T.G.; Vittori, S.; Perry, J.A.; Qi, J.; Winter, G.E.; Wong, K.K.; Gray, N.S.; Bradner, J.E. The dTAG system for immediate and target-specific protein degradation. Nat. Chem. Biol., 2018, 14(5), 431-441.
[http://dx.doi.org/10.1038/s41589-018-0021-8] [PMID: 29581585]
[95]
Leus, N.G.; Zwinderman, M.R.; Dekker, F.J. Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation. Curr. Opin. Chem. Biol., 2016, 33, 160-168.
[http://dx.doi.org/10.1016/j.cbpa.2016.06.019] [PMID: 27371876]
[96]
Leus, N.G.; van der Wouden, P.E.; van den Bosch, T.; Hooghiemstra, W.T.R.; Ourailidou, M.E.; Kistemaker, L.E.; Bischoff, R.; Gosens, R.; Haisma, H.J.; Dekker, F.J. HDAC 3-selective inhibitor RGFP966 demonstrates anti-inflammatory properties in RAW 264.7 macrophages and mouse precision-cut lung slices by attenuating NF-kappaB p65 transcriptional activity. Biochem. Pharmacol. (Amsterdam, Neth.), 2016, 108, 58-74.
[97]
Giridharan, S.; Srinivasan, M. Mechanisms of NF-κB p65 and strategies for therapeutic manipulation. J. Inflamm. Res., 2018, 11, 407-419.
[http://dx.doi.org/10.2147/JIR.S140188] [PMID: 30464573]
[98]
Cao, F.; Zwinderman, M.R.H.; van Merkerk, R.; Ettema, P.E.; Quax, W.J.; Dekker, F.J. Inhibitory selectivity among class I HDACs has a major impact on inflammatory gene expression in macrophages. Eur. J. Med. Chem., 2019, 177, 457-466.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.038] [PMID: 31181405]
[99]
Cao, F.; de Weerd, S.; Chen, D.; Zwinderman, M.R.H.; van der Wouden, P.E.; Dekker, F.J. Induced protein degradation of Histone Deacetylases 3 (HDAC3) by proteolysis targeting chimera (PROTAC). Eur. J. Med. Chem., 2020, 208, 112800.
[http://dx.doi.org/10.1016/j.ejmech.2020.112800] [PMID: 32971411]
[100]
Beckers, T.; Burkhardt, C.; Wieland, H.; Gimmnich, P.; Ciossek, T.; Maier, T.; Sanders, K. Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int. J. Cancer, 2007, 121(5), 1138-1148.
[http://dx.doi.org/10.1002/ijc.22751] [PMID: 17455259]
[101]
Lauffer, B.E.; Mintzer, R.; Fong, R.; Mukund, S.; Tam, C.; Zilberleyb, I.; Flicke, B.; Ritscher, A.; Fedorowicz, G.; Vallero, R.; Ortwine, D.F.; Gunzner, J.; Modrusan, Z.; Neumann, L.; Koth, C.M.; Lupardus, P.J.; Kaminker, J.S.; Heise, C.E.; Steiner, P. Histone deacetylase (HDAC) inhibitor kinetic rate constants correlate with cellular histone acetylation but not transcription and cell viability. J. Biol. Chem., 2013, 288(37), 26926-26943.
[http://dx.doi.org/10.1074/jbc.M113.490706] [PMID: 23897821]
[102]
Wagner, F.F.; Lundh, M.; Kaya, T.; McCarren, P.; Zhang, Y.L.; Chattopadhyay, S.; Gale, J.P.; Galbo, T.; Fisher, S.L.; Meier, B.C.; Vetere, A.; Richardson, S.; Morgan, N.G.; Christensen, D.P.; Gilbert, T.J.; Hooker, J.M.; Leroy, M.; Walpita, D.; Mandrup-Poulsen, T.; Wagner, B.K.; Holson, E.B. An isochemogenic set of inhibitors to define the therapeutic potential of histone deacetylases in β-cell protection. ACS Chem. Biol., 2016, 11(2), 363-374.
[http://dx.doi.org/10.1021/acschembio.5b00640] [PMID: 26640968]
[103]
Smalley, J.P.; Adams, G.E.; Millard, C.J.; Song, Y.; Norris, J.K.S.; Schwabe, J.W.R.; Cowley, S.M.; Hodgkinson, J.T. PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes. Chem. Commun. (Camb.), 2020, 56(32), 4476-4479.
[http://dx.doi.org/10.1039/D0CC01485K] [PMID: 32201871]
[104]
Wang, Y.; Stowe, R.L.; Pinello, C.E.; Tian, G.; Madoux, F.; Li, D.; Zhao, L.Y.; Li, J.L.; Wang, Y.; Wang, Y.; Ma, H.; Hodder, P.; Roush, W.R.; Liao, D. Identification of histone deacetylase inhibitors with benzoylhydrazide scaffold that selectively inhibit class I histone deacetylases. Chem. Biol., 2015, 22(2), 273-284.
[http://dx.doi.org/10.1016/j.chembiol.2014.12.015] [PMID: 25699604]
[105]
Xiao, Y.; Wang, J.; Zhao, L.Y.; Chen, X.; Zheng, G.; Zhang, X.; Liao, D. Discovery of histone deacetylase 3 (HDAC3)-specific PROTACs. Chem. Commun. (Camb.), 2020, 56(68), 9866-9869.
[http://dx.doi.org/10.1039/D0CC03243C] [PMID: 32840532]
[106]
Sun, Z.; Feng, D.; Fang, B.; Mullican, S.E.; You, S.H.; Lim, H.W.; Everett, L.J.; Nabel, C.S.; Li, Y.; Selvakumaran, V.; Won, K.J.; Lazar, M.A. Deacetylase-independent function of HDAC3 in transcription and metabolism requires nuclear receptor corepressor. Mol. Cell, 2013, 52(6), 769-782.
[http://dx.doi.org/10.1016/j.molcel.2013.10.022] [PMID: 24268577]
[107]
Thota, S.; Rodrigues, D.A.; Pinheiro, P.S.M.; Lima, L.M.; Fraga, C.A.M.; Barreiro, E.J. N-Acylhydrazones as drugs. Bioorg. Med. Chem. Lett., 2018, 28(17), 2797-2806.
[http://dx.doi.org/10.1016/j.bmcl.2018.07.015] [PMID: 30006065]
[108]
Tang, W.; Luo, T.; Greenberg, E.F.; Bradner, J.E.; Schreiber, S.L. Discovery of histone deacetylase 8 selective inhibitors. Bioorg. Med. Chem. Lett., 2011, 21(9), 2601-2605.
[http://dx.doi.org/10.1016/j.bmcl.2011.01.134] [PMID: 21334896]
[109]
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]
[110]
Bergman, J.A.; Woan, K.; Perez-Villarroel, P.; Villagra, A.; Sotomayor, E.M.; Kozikowski, A.P. Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth. J. Med. Chem., 2012, 55(22), 9891-9899.
[http://dx.doi.org/10.1021/jm301098e] [PMID: 23009203]
[111]
Miyake, Y.; Keusch, J.J.; Wang, L.; Saito, M.; Hess, D.; Wang, X.; Melancon, B.J.; Helquist, P.; Gut, H.; Matthias, P. Structural insights into HDAC6 tubulin deacetylation and its selective inhibition. Nat. Chem. Biol., 2016, 12(9), 748-754.
[http://dx.doi.org/10.1038/nchembio.2140] [PMID: 27454931]
[112]
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.
[http://dx.doi.org/10.1038/leu.2012.119] [PMID: 22552008]
[113]
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.
[http://dx.doi.org/10.1126/science.1177319] [PMID: 20223979]
[114]
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.
[http://dx.doi.org/10.1126/science.1244851] [PMID: 24292625]
[115]
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.
[http://dx.doi.org/10.1126/science.1244917] [PMID: 24292623]
[116]
Xia, L.W.; Ba, M.Y.; Liu, W.; Cheng, W.; Hu, C.P.; Zhao, Q.; Yao, Y.F.; Sun, M.R.; Duan, Y.T. Triazol: a privileged scaffold for proteolysis targeting chimeras. Future Med. Chem., 2019, 11(22), 2919-2973.
[http://dx.doi.org/10.4155/fmc-2019-0159] [PMID: 31702389]
[117]
Yang, H.; Lv, W.; He, M.; Deng, H.; Li, H.; Wu, W.; Rao, Y. Plasticity in designing PROTACs for selective and potent degradation of HDAC6. Chem. Commun. (Camb.), 2019, 55(98), 14848-14851.
[http://dx.doi.org/10.1039/C9CC08509B] [PMID: 31769449]
[118]
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.
[http://dx.doi.org/10.1038/nature13527] [PMID: 25043012]
[119]
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]
[120]
Yang, K.; Zhao, Y.; Nie, X.; Wu, H.; Wang, B.; Almodovar-Rivera, C.M.; Xie, H.; Tang, W. A cell-based target engagement assay for the identification of cereblon E3 ubiquitin ligase ligands and their application in HDAC6 degraders. Cell Chem. Biol., 2020, 27(7), 866-876.e8.
[http://dx.doi.org/10.1016/j.chembiol.2020.04.008] [PMID: 32413286]
[121]
Hu, J.; Hu, B.; Wang, M.; Xu, F.; Miao, B.; Yang, C.Y.; Wang, M.; Liu, Z.; Hayes, D.F.; Chinnaswamy, K.; Delproposto, J.; Stuckey, J.; Wang, S. Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) degrader of Estrogen Receptor (ER). J. Med. Chem., 2019, 62(3), 1420-1442.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01572] [PMID: 30990042]
[122]
Smith, B.E.; Wang, S.L.; Jaime-Figueroa, S.; Harbin, A.; Wang, J.; Hamman, B.D.; Crews, C.M. Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase. Nat. Commun., 2019, 10(1), 131.
[http://dx.doi.org/10.1038/s41467-018-08027-7] [PMID: 30631068]
[123]
Olson, D.E.; Wagner, F.F.; Kaya, T.; Gale, J.P.; Aidoud, N.; Davoine, E.L.; Lazzaro, F.; Weïwer, M.; Zhang, Y.L.; Holson, E.B. Discovery of the first histone deacetylase 6/8 dual inhibitors. J. Med. Chem., 2013, 56(11), 4816-4820.
[http://dx.doi.org/10.1021/jm400390r] [PMID: 23672185]
[124]
Cao, J.; Zhao, W.; Zhao, C.; Liu, Q.; Li, S.; Zhang, G.; Chou, C.J.; Zhang, Y. Development of a Bestatin-SAHA hybrid with dual inhibitory activity against APN and HDAC. Molecules, 2020, 25(21), E4991.
[http://dx.doi.org/10.3390/molecules25214991] [PMID: 33126591]
[125]
Sinatra, L.; Bandolik, J.J.; Roatsch, M.; Sönnichsen, M.; Schoeder, C.T.; Hamacher, A.; Schöler, A.; Borkhardt, A.; Meiler, J.; Bhatia, S.; Kassack, M.U.; Hansen, F.K. Hydroxamic Acids Immobilized on Resins (HAIRs): synthesis of dual-targeting HDAC inhibitors and HDAC Degraders (PROTACs). Angew. Chem. Int. Ed. Engl., 2020, 59(50), 22494-22499.
[http://dx.doi.org/10.1002/anie.202006725] [PMID: 32780485]
[126]
Pike, A.; Williamson, B.; Harlfinger, S.; Martin, S.; McGinnity, D.F. Optimising proteolysis-targeting chimeras (PROTACs) for oral drug delivery: a drug metabolism and pharmacokinetics perspective. Drug Discov. Today, 2020, 25, 1793-1800.
[http://dx.doi.org/10.1016/j.drudis.2020.07.013] [PMID: 32693163]
[127]
Goracci, L.; Desantis, J.; Valeri, A.; Castellani, B.; Eleuteri, M.; Cruciani, G. Understanding the Metabolism of Proteolysis Targeting Chimeras (PROTACs): The Next Step toward Pharmaceutical Applications. J. Med. Chem., 2020, 63(20), 11615-11638.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00793] [PMID: 33026811]
[128]
Klein, V.G.; Townsend, C.E.; Testa, A.; Zengerle, M.; Maniaci, C.; Hughes, S.J.; Chan, K.H.; Ciulli, A.; Lokey, R.S. Understanding and improving the membrane permeability of VH032-based PROTACs. ACS Med. Chem. Lett., 2020, 11(9), 1732-1738.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00265] [PMID: 32939229]
[129]
Neklesa, T.; Snyder, L.B.; Willard, R.R.; Vitale, N.; Raina, K.; Pizzano, J.; Gordon, D.A.; Bookbinder, M.; Macaluso, J.; Dong, H.; Liu, Z.; Ferraro, C.; Wang, G.; Wang, J.; Crews, C.M.; Houston, J.; Crew, A.P.; Taylor, I. An oral androgen receptor PROTAC degrader for prostate cancer. J. Clin. Oncol., 2018, 36(6)(Suppl.), 381.
[http://dx.doi.org/10.1200/JCO.2018.36.6_suppl.381]
[130]
Wei, M.; Zhao, R.; Cao, Y.; Wei, Y.; Li, M.; Dong, Z.; Liu, Y.; Ruan, H.; Li, Y.; Cao, S.; Tang, Z.; Zhou, Y.; Song, W.; Wang, Y.; Wang, J.; Yang, G.; Yang, C. First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo. Eur. J. Med. Chem., 2021, 209, 112903.
[http://dx.doi.org/10.1016/j.ejmech.2020.112903] [PMID: 33256948]

Rights & Permissions Print Cite
Article Metrics
61
1
© 2024 Bentham Science Publishers | Privacy Policy