Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Medicinal Chemistry
  4. Fast Track Articles
  5. Fast Track Article
image of Structural Modifications and Prospects of Histone Deacetylase (HDAC) Inhibitors in Cancer

Abstract

Histone deacetylases (HDACs) play a crucial role in the regulation of cancer progression and have emerged as key targets for antitumor therapy. Histone Deacetylase Inhibitors (HDACis) effectively suppress tumor cell proliferation, induce apoptosis, and cause cell cycle arrest, demonstrating broad-spectrum antitumor activity. This article primarily focuses on enhancing the selectivity of HDACis through structural modification using natural compounds. It provides detailed insights into the structure modification of histone deacetylase 8 (HDAC8) and histone deacetylase 10 (HDAC10), as well as dual- target inhibitors and their pharmacological effects. Furthermore, conventional HDAC inhibitors are susceptible to off-target effects and the development of drug resistance. Our research focuses on augmenting the targeting specificity of HDAC inhibitors through their combination with proteolysis targeting chimera (PROTAC). Lastly, the latest advancements in clinical research on HDAC inhibitors were summarized, revealing that these inhibitors possess limitations in their clinical applications due to intrinsic or acquired resistance. Consequently, this article primarily focuses on summarizing the current status and prospects of structural modifications for HDAC inhibitors, with the aim of inspiring researchers to develop novel HDAC inhibitors exhibiting enhanced activity for improved application in clinical research.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673332285241104091609
2025-01-09
2025-05-30

  • From This Site

    /content/journals/cmc/10.2174/0109298673332285241104091609
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Liang T. Wang F. Elhassan R.M. Cheng Y. Tang X. Chen W. Fang H. Hou X. Targeting histone deacetylases for cancer therapy: Trends and challenges. Acta Pharm. Sin. B 2023 13 6 2425 2463 10.1016/j.apsb.2023.02.007 37425042
    [Google Scholar]
  2. Cheng B. Pan W. Xiao Y. Ding Z. Zhou Y. Fei X. Liu J. Su Z. Peng X. Chen J. HDAC-targeting epigenetic modulators for cancer immunotherapy. Eur. J. Med. Chem. 2024 265 116129 10.1016/j.ejmech.2024.116129 38211468
    [Google Scholar]
  3. Parveen R. Harihar D. Chatterji B.P. Recent histone deacetylase inhibitors in cancer therapy. Cancer 2023 129 21 3372 3380 10.1002/cncr.34974 37560925
    [Google Scholar]
  4. Liu Y.M. Liou J.P. An updated patent review of histone deacetylase (HDAC) inhibitors in cancer (2020 – present). Expert Opin. Ther. Pat. 2023 33 5 349 369 10.1080/13543776.2023.2219393 37249104
    [Google Scholar]
  5. Serrano L. Martínez-Redondo P. Marazuela-Duque A. Vazquez B.N. Dooley S.J. Voigt P. Beck D.B. Kane- Goldsmith N. Tong Q. Rabanal R.M. Fondevila D. Muñoz P. Krüger M. Tischfield J.A. Vaquero A. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation. Genes Dev. 2013 27 6 639 653 10.1101/gad.211342.112 23468428
    [Google Scholar]
  6. Yanginlar C. Logie C. HDAC11 is a regulator of diverse immune functions. Biochim. Biophys. Acta. Gene Regul. Mech. 2018 1861 1 54 59 10.1016/j.bbagrm.2017.12.002 29222071
    [Google Scholar]
  7. Verdin E. Dequiedt F. Kasler H.G. Class II histone deacetylases: Versatile regulators. Trends Genet. 2003 19 5 286 293 10.1016/S0168‑9525(03)00073‑8 12711221
    [Google Scholar]
  8. Seto E. Yoshida M. Erasers of histone acetylation: The histone deacetylase enzymes. Cold Spring Harb. Perspect. Biol. 2014 6 4 a018713 10.1101/cshperspect.a018713 24691964
    [Google Scholar]
  9. Dang F. Wei W. Targeting the acetylation signaling pathway in cancer therapy. Semin. Cancer Biol. 2022 85 209 218 10.1016/j.semcancer.2021.03.001 33705871
    [Google Scholar]
  10. Neganova M.E. Klochkov S.G. Aleksandrova Y.R. Aliev G. Histone modifications in epigenetic regulation of cancer: Perspectives and achieved progress. Semin. Cancer Biol. 2022 83 452 471 10.1016/j.semcancer.2020.07.015 32814115
    [Google Scholar]
  11. Di Cerbo V. Schneider R. Cancers with wrong HATs: The impact of acetylation. Brief. Funct. Genomics 2013 12 3 231 243 10.1093/bfgp/els065 23325510
    [Google Scholar]
  12. Kouzarides T. Chromatin modifications and their function. Cell 2007 128 4 693 705 10.1016/j.cell.2007.02.005 17320507
    [Google Scholar]
  13. Ho T.C.S. Chan A.H.Y. Ganesan A. Thirty years of HDAC inhibitors: 2020 insight and hindsight. J. Med. Chem. 2020 63 21 12460 12484 10.1021/acs.jmedchem.0c00830 32608981
    [Google Scholar]
  14. Zhao A. Zhou H. Yang J. Li M. Niu T. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies. Signal Transduct. Target. Ther. 2023 8 1 71 10.1038/s41392‑023‑01342‑6 36797244
    [Google Scholar]
  15. Willhoft O. Costa A. A structural framework for DNA replication and transcription through chromatin. Curr. Opin. Struct. Biol. 2021 71 51 58 10.1016/j.sbi.2021.05.008 34218162
    [Google Scholar]
  16. Nitsch S. Zorro Shahidian L. Schneider R. Histone acylations and chromatin dynamics: Concepts, challenges, and links to metabolism. EMBO Rep. 2021 22 7 e52774 10.15252/embr.202152774 34159701
    [Google Scholar]
  17. Li B. Carey M. Workman J.L. The role of chromatin during transcription. Cell 2007 128 4 707 719 10.1016/j.cell.2007.01.015 17320508
    [Google Scholar]
  18. Eckschlager T. Plch J. Stiborova M. Hrabeta J. Histone deacetylase inhibitors as anticancer drugs. Int. J. Mol. Sci. 2017 18 7 1414 10.3390/ijms18071414 28671573
    [Google Scholar]
  19. Li G. Tian Y. Zhu W.G. The roles of histone deacetylases and their inhibitors in cancer therapy. Front. Cell Dev. Biol. 2020 8 576946 10.3389/fcell.2020.576946 33117804
    [Google Scholar]
  20. Karati D. Mukherjee S. Roy S. Emerging therapeutic strategies in cancer therapy by HDAC inhibition as the chemotherapeutic potent and epigenetic regulator. Med. Oncol. 2024 41 4 84 10.1007/s12032‑024‑02303‑x 38438564
    [Google Scholar]
  21. Kim Y.B. Ki S.W. Yosnida M. Horinouchi S. Mechanism of cell cycle arrest caused by histone deacetylase inhibitors in human carcinoma cells. J. Antibiot. (Tokyo) 2000 53 10 1191 1200 10.7164/antibiotics.53.1191 11132966
    [Google Scholar]
  22. Chun P. Histone deacetylase inhibitors in hematological malignancies and solid tumors. Arch. Pharm. Res. 2015 38 6 933 949 10.1007/s12272‑015‑0571‑1 25653088
    [Google Scholar]
  23. Su B. Lim D. Qi C. Zhang Z. Wang J. Zhang F. Dong C. Feng Z. VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU. Cell Death Dis. 2023 14 2 114 10.1038/s41419‑023‑05649‑8 36781846
    [Google Scholar]
  24. Gong P. Wang Y. Jing Y. Apoptosis induction byHistone deacetylase inhibitors in cancer cells: Role of Ku70. Int. J. Mol. Sci. 2019 20 7 1601 10.3390/ijms20071601 30935057
    [Google Scholar]
  25. Zhang J. Zhong Q. Histone deacetylase inhibitors and cell death. Cell. Mol. Life Sci. 2014 71 20 3885 3901 10.1007/s00018‑014‑1656‑6 24898083
    [Google Scholar]
  26. Liu Y.L. Yang P.M. Shun C.T. Wu M.S. Weng J.R. Chen C.C. Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma. Autophagy 2010 6 8 1057 1065 10.4161/auto.6.8.13365 20962572
    [Google Scholar]
  27. Sykes S.M. Mellert H.S. Holbert M.A. Li K. Marmorstein R. Lane W.S. McMahon S.B. Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol. Cell 2006 24 6 841 851 10.1016/j.molcel.2006.11.026 17189187
    [Google Scholar]
  28. Watanabe M. Adachi S. Matsubara H. Imai T. Yui Y. Mizushima Y. Hiraumi Y. Watanabe K. Kamitsuji Y. Toyokuni S. Hosoi H. Sugimoto T. Toguchida J. Nakahata T. Induction of autophagy in malignant rhabdoid tumor cells by the histone deacetylase inhibitor FK228 through AIF translocation. Int. J. Cancer 2009 124 1 55 67 10.1002/ijc.23897 18821579
    [Google Scholar]
  29. Stengel K.R. Hiebert S.W. Class I. Class I HDACs affect DNA replication, repair, and chromatin structure: Implications for cancer therapy. Antioxid. Redox Signal. 2015 23 1 51 65 10.1089/ars.2014.5915 24730655
    [Google Scholar]
  30. Nishida N. Yano H. Nishida T. Kamura T. Kojiro M. Angiogenesis in cancer. Vasc. Health Risk Manag. 2006 2 3 213 219 10.2147/vhrm.2006.2.3.213 17326328
    [Google Scholar]
  31. Zecchin A. Pattarini L. Gutierrez M.I. Mano M. Mai A. Valente S. Myers M.P. Pantano S. Giacca M. Reversible acetylation regulates vascular endothelial growth factor receptor-2 activity. J. Mol. Cell Biol. 2014 6 2 116 127 10.1093/jmcb/mju010 24620033
    [Google Scholar]
  32. Li B. Chan H.L. Chen P. Immune checkpoint inhibitors: Basics and challenges. Curr. Med. Chem. 2019 26 17 3009 3025 10.2174/0929867324666170804143706 28782469
    [Google Scholar]
  33. Blaszczak W. Liu G. Zhu H. Barczak W. Shrestha A. Albayrak G. Zheng S. Kerr D. Samsonova A. La Thangue N.B. Immune modulation underpins the anti- cancer activity of HDAC inhibitors. Mol. Oncol. 2021 15 12 3280 3298 10.1002/1878‑0261.12953 33773029
    [Google Scholar]
  34. Gao Y. Nihira N.T. Bu X. Chu C. Zhang J. Kolodziejczyk A. Fan Y. Chan N.T. Ma L. Liu J. Wang D. Dai X. Liu H. Ono M. Nakanishi A. Inuzuka H. North B.J. Huang Y.H. Sharma S. Geng Y. Xu W. Liu X.S. Li L. Miki Y. Sicinski P. Freeman G.J. Wei W. Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy. Nat. Cell Biol. 2020 22 9 1064 1075 10.1038/s41556‑020‑0562‑4 32839551
    [Google Scholar]
  35. Juengel E. Makarević J. Tsaur I. Bartsch G. Nelson K. Haferkamp A. Blaheta R.A. Resistance after chronic application of the HDAC-inhibitor valproic acid is associated with elevated Akt activation in renal cell carcinoma in vivo. PLoS One 2013 8 1 e53100 10.1371/journal.pone.0053100 23372654
    [Google Scholar]
  36. Hay N. Reprogramming glucose metabolism in cancer: Can it be exploited for cancer therapy? Nat. Rev. Cancer 2016 16 10 635 649 10.1038/nrc.2016.77 27634447
    [Google Scholar]
  37. Lin X. Xiao Z. Chen T. Liang S.H. Guo H. Glucose metabolism on tumor plasticity, diagnosis, and treatment. Front. Oncol. 2020 10 317 10.3389/fonc.2020.00317 32211335
    [Google Scholar]
  38. Yucel N. Wang Y.X. Mai T. Porpiglia E. Lund P.J. Markov G. Garcia B.A. Bendall S.C. Angelo M. Blau H.M. Glucose metabolism drives Histone Acetylation landscape transitions that dictate muscle stem cell function. Cell Rep. 2019 27 13 3939 3955.e6 10.1016/j.celrep.2019.05.092 31242425
    [Google Scholar]
  39. Zhang R. Shen M. Wu C. Chen Y. Lu J. Li J. Zhao L. Meng H. Zhou X. Huang G. Zhao X. Liu J. HDAC8-dependent deacetylation of PKM2 directs nuclear localization and glycolysis to promote proliferation in hepatocellular carcinoma. Cell Death Dis. 2020 11 12 1036 10.1038/s41419‑020‑03212‑3 33279948
    [Google Scholar]
  40. Negrini S. Gorgoulis V.G. Halazonetis T.D. Genomic instability — an evolving hallmark of cancer. Nat. Rev. Mol. Cell Biol. 2010 11 3 220 228 10.1038/nrm2858 20177397
    [Google Scholar]
  41. Hanahan D. Weinberg R.A. Hallmarks of cancer: The next generation. Cell 2011 144 5 646 674 10.1016/j.cell.2011.02.013 21376230
    [Google Scholar]
  42. Yano M. Miyazawa M. Ogane N. Ogasawara A. Hasegawa K. Narahara H. Yasuda M. Up-regulation of HDAC6 results in poor prognosis and chemoresistance in patients with advanced ovarian high-grade serous Carcinoma. Anticancer Res. 2021 41 3 1647 1654 10.21873/anticanres.14927 33788761
    [Google Scholar]
  43. Zhou L. Xu X. Liu H. Hu X. Zhang W. Ye M. Zhu X. Prognosis analysis of histone Deacetylases mRNA Expression in ovarian cancer patients. J. Cancer 2018 9 23 4547 4555 10.7150/jca.26780 30519361
    [Google Scholar]
  44. Shen Y.F. Wei A.M. Kou Q. Zhu Q.Y. Zhang L. Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices. Oncol. Rep. 2016 35 2 948 954 10.3892/or.2015.4423 26572940
    [Google Scholar]
  45. Roos W.P. Krumm A. The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair. Nucleic Acids Res. 2016 44 21 gkw922 10.1093/nar/gkw922 27738139
    [Google Scholar]
  46. Biersack B. Polat S. Höpfner M. Anticancer properties of chimeric HDAC and kinase inhibitors. Semin. Cancer Biol. 2022 83 472 486 10.1016/j.semcancer.2020.11.005 33189849
    [Google Scholar]
  47. Zhang X.H. Qin-Ma Wu H.P. Khamis M.Y. Li Y.H. Ma L.Y. Liu H.M. A review of progress in Histone Deacetylase 6 inhibitors research: Structural specificity and functional diversity. J. Med. Chem. 2021 64 3 1362 1391 10.1021/acs.jmedchem.0c01782 33523672
    [Google Scholar]
  48. Li Y. Wang F. Chen X. Wang J. Zhao Y. Li Y. He B. Zinc-dependent Deacetylase (HDAC) inhibitors with different Zinc binding groups. Curr. Top. Med. Chem. 2019 19 3 223 241 10.2174/1568026619666190122144949 30674261
    [Google Scholar]
  49. Ververis K. Hiong A. Karagiannis T.C. Licciardi P.V. Histone deacetylase inhibitors (HDACIs): Multitargeted anticancer agents. Biologics 2013 7 47 60 23459471
    [Google Scholar]
  50. Ru J. Wang Y. Li Z. Wang J. Ren C. Zhang J. Technologies of targeting histone deacetylase in drug discovery: Current progress and emerging prospects. Eur. J. Med. Chem. 2023 261 115800 10.1016/j.ejmech.2023.115800 37708798
    [Google Scholar]
  51. Lian B. Chen X. Shen K. Inhibition of histone deacetylases attenuates tumor progression and improves immunotherapy in breast cancer. Front. Immunol. 2023 14 1164514 10.3389/fimmu.2023.1164514 36969235
    [Google Scholar]
  52. Rajaselvi N.D. Jida M.D. Ajeeshkumar K.K. Nair S.N. John P. Aziz Z. Nisha A.R. Antineoplastic activity of plant-derived compounds mediated through inhibition of histone deacetylase: A review. Amino Acids 2023 55 12 1803 1817 10.1007/s00726‑023‑03298‑x 37389730
    [Google Scholar]
  53. Bian J. luan Y. Wang C. Zhang L. Discovery of N-hydroxy-4-(1H-indol-3-yl)butanamide as a histone deacetylase inhibitor. Drug Discov. Ther. 2016 10 3 163 166 10.5582/ddt.2016.01031 27169369
    [Google Scholar]
  54. Chen Y. Zhang L. Zhang L. Jiang Q. Zhang L. Discovery of indole-3-butyric acid derivatives as potent histone deacetylase inhibitors. J. Enzyme Inhib. Med. Chem. 2021 36 1 425 436 10.1080/14756366.2020.1870457 33445997
    [Google Scholar]
  55. Lee H.Y. Chang C.Y. Su C.J. Huang H.L. Mehndiratta S. Chao Y.H. Hsu C.M. Kumar S. Sung T.Y. Huang Y.Z. Li Y.H. Yang C.R. Liou J.P. 2-(Phenylsulfonyl)quinoline N -hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase. Eur. J. Med. Chem. 2016 122 92 101 10.1016/j.ejmech.2016.06.023 27344487
    [Google Scholar]
  56. Lee H.Y. Nepali K. Huang F.I. Chang C.Y. Lai M.J. Li Y.H. Huang H.L. Yang C.R. Liou J.P. ( N -Hydroxycarbonylbenylamino)quinolines as selective Histone Deacetylase 6 inhibitors suppress growth of multiple Myeloma in vitro and in vivo. J. Med. Chem. 2018 61 3 905 917 10.1021/acs.jmedchem.7b01404 29304284
    [Google Scholar]
  57. Mehndiratta S. Chen M.C. Chao Y.H. Lee C.H. Liou J.P. Lai M.J. Lee H.Y. Effect of 3-subsitution of quinolinehydroxamic acids on selectivity of histone deacetylase isoforms. J. Enzyme Inhib. Med. Chem. 2021 36 1 74 84 10.1080/14756366.2020.1839446 33161799
    [Google Scholar]
  58. Yao D. Li C. Jiang J. Huang J. Wang J. He Z. Zhang J. Design, synthesis and biological evaluation of novel HDAC inhibitors with improved pharmacokinetic profile in breast cancer. Eur. J. Med. Chem. 2020 205 112648 10.1016/j.ejmech.2020.112648 32791401
    [Google Scholar]
  59. Zhang S.W. Gong C.J. Su M.B. Chen F. He T. Zhang Y.M. Shen Q.Q. Su Y. Ding J. Li J. Chen Y. Nan F.J. Synthesis and in vitro and in vivo biological evaluation of tissue-specific Bisthiazole Histone Deacetylase (HDAC) inhibitors. J. Med. Chem. 2020 63 2 804 815 10.1021/acs.jmedchem.9b01792 31855601
    [Google Scholar]
  60. Zhao Y. Yao Z. Ren W. Yang X. Hou X. Cao S. Fang H. Design, synthesis and bioactivity evaluations of 8-substituted-quinoline-2-carboxamide derivatives as novel histone deacetylase (HDAC) inhibitors. Bioorg. Med. Chem. 2023 85 117242 10.1016/j.bmc.2023.117242 37079967
    [Google Scholar]
  61. Chen X. Ding X. Fang J. Mao C. Gong X. Zhang Y. Zhang N. Yan F. Lou Y. Chen Z. Ding W. Ma Z. Natural derivatives of selective HDAC8 inhibitors with potent in Vivo antitumor efficacy against breast cancer. J. Med. Chem. 2024 67 16 14609 14632 10.1021/acs.jmedchem.4c01438 39110628
    [Google Scholar]
  62. Zhu S. Zhu W. Zhao K. Yu J. Lu W. Zhou R. Fan S. Kong W. Yang F. Shan P. Discovery of a novel hybrid coumarin-hydroxamate conjugate targeting the HDAC1-Sp1-FOSL2 signaling axis for breast cancer therapy. Cell Commun. Signal. 2024 22 1 361 10.1186/s12964‑024‑01733‑4 39010083
    [Google Scholar]
  63. Omidkhah N. Ghodsi R. NO-HDAC dual inhibitors. Eur. J. Med. Chem. 2022 227 113934 10.1016/j.ejmech.2021.113934 34700268
    [Google Scholar]
  64. Bass A.K.A. El-Zoghbi M.S. Nageeb E.S.M. Mohamed M.F.A. Badr M. Abuo-Rahma G.E.D.A. Comprehensive review for anticancer hybridized multitargeting HDAC inhibitors. Eur. J. Med. Chem. 2021 209 112904 10.1016/j.ejmech.2020.112904 33077264
    [Google Scholar]
  65. Fu R. Sun Y. Sheng W. Liao D. Designing multi-targeted agents: An emerging anticancer drug discovery paradigm. Eur. J. Med. Chem. 2017 136 195 211 10.1016/j.ejmech.2017.05.016 28494256
    [Google Scholar]
  66. Choudhary G.S. Al-harbi S. Mazumder S. Hill B.T. Smith M.R. Bodo J. Hsi E.D. Almasan A. MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies. Cell Death Dis. 2015 6 1 e1593 10.1038/cddis.2014.525 25590803
    [Google Scholar]
  67. Bailly C. Contemporary challenges in the design of topoisomerase II inhibitors for cancer chemotherapy. Chem. Rev. 2012 112 7 3611 3640 10.1021/cr200325f 22397403
    [Google Scholar]
  68. Zhang W.X. Huang J. Tian X.Y. Liu Y.H. Jia M.Q. Wang W. Jin C.Y. Song J. Zhang S.Y. A review of progress in o-aminobenzamide-based HDAC inhibitors with dual targeting capabilities for cancer therapy. Eur. J. Med. Chem. 2023 259 115673 10.1016/j.ejmech.2023.115673 37487305
    [Google Scholar]
  69. Roy R. Ria T. RoyMahaPatra D. Sk U.H. Single inhibitors versus dual inhibitors: Role of HDAC in cancer. ACS Omega 2023 8 19 16532 16544 10.1021/acsomega.3c00222 37214715
    [Google Scholar]
  70. Vanhaesebroeck B. Guillermet-Guibert J. Graupera M. Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat. Rev. Mol. Cell Biol. 2010 11 5 329 341 10.1038/nrm2882 20379207
    [Google Scholar]
  71. Thakur A. Tawa G.J. Henderson M.J. Danchik C. Liu S. Shah P. Wang A.Q. Dunn G. Kabir M. Padilha E.C. Xu X. Simeonov A. Kharbanda S. Stone R. Grewal G. Design, synthesis, and biological evaluation of Quinazolin-4-one-based Hydroxamic acids as dual PI3K/HDAC inhibitors. J. Med. Chem. 2020 63 8 4256 4292 10.1021/acs.jmedchem.0c00193 32212730
    [Google Scholar]
  72. Zhang K. Lai F. Lin S. Ji M. Zhang J. Zhang Y. Jin J. Fu R. Wu D. Tian H. Xue N. Sheng L. Zou X. Li Y. Chen X. Xu H. Design, synthesis, and biological evaluation of 4-methyl quinazoline derivatives as anticancer agents simultaneously targeting phosphoinositide 3-kinases and histone deacetylases. J. Med. Chem. 2019 62 15 6992 7014 10.1021/acs.jmedchem.9b00390 31117517
    [Google Scholar]
  73. Blazek D. Therapeutic potential of CDK11 in cancer. Clin. Transl. Med. 2023 13 3 e1201 10.1002/ctm2.1201 36855776
    [Google Scholar]
  74. Cheng C. Yun F. Ullah S. Yuan Q. Discovery of novel cyclin-dependent kinase (CDK) and histone deacetylase (HDAC) dual inhibitors with potent in vitro and in vivo anticancer activity. Eur. J. Med. Chem. 2020 189 112073 10.1016/j.ejmech.2020.112073 31991336
    [Google Scholar]
  75. Yu Y. Ran D. Jiang J. Pan T. Dan Y. Tang Q. Li W. Zhang L. Gan L. Gan Z. Discovery of novel 9H-purin derivatives as dual inhibitors of HDAC1 and CDK2. Bioorg. Med. Chem. Lett. 2019 29 16 2136 2140 10.1016/j.bmcl.2019.06.059 31272794
    [Google Scholar]
  76. Zubair T. Bandyopadhyay D. Small molecule EGFR inhibitors as anti-cancer agents: discovery, mechanisms of action, and opportunities. Int. J. Mol. Sci. 2023 24 3 2651 10.3390/ijms24032651 36768973
    [Google Scholar]
  77. Goehringer N. Biersack B. Peng Y. Schobert R. Herling M. Ma A. Nitzsche B. Höpfner M. Anticancer activity and mechanisms of action of new chimeric EGFR/HDAC-inhibitors. Int. J. Mol. Sci. 2021 22 16 8432 10.3390/ijms22168432 34445133
    [Google Scholar]
  78. Wickner S. Nguyen T.L.L. Genest O. The bacterial Hsp90 Chaperone: Cellular functions and mechanism of action. Annu. Rev. Microbiol. 2021 75 1 719 739 10.1146/annurev‑micro‑032421‑035644 34375543
    [Google Scholar]
  79. Wang L. Zhang Q. You Q. Targeting the HSP90–CDC37–kinase chaperone cycle: A promising therapeutic strategy for cancer. Med. Res. Rev. 2022 42 1 156 182 10.1002/med.21807 33846988
    [Google Scholar]
  80. Chowdhury S.R. Koley T. Singh M. Ethayathulla A.S. Kaur P. Association of Hsp90 with p53 and fizzy related homolog (Fzr) synchronizing anaphase promoting complex (APC/C): An unexplored ally towards oncogenic pathway. Biochim. Biophys. Acta Rev. Cancer 2023 1878 3 188883 10.1016/j.bbcan.2023.188883 36972769
    [Google Scholar]
  81. Dernovšek J. Tomašič T. Following the design path of isoform-selective Hsp90 inhibitors: Small differences, great opportunities. Pharmacol. Ther. 2023 245 108396 10.1016/j.pharmthera.2023.108396 37001734
    [Google Scholar]
  82. Youssef M.E. Cavalu S. Hasan A.M. Yahya G. Abd-Eldayem M.A. Saber S. Role of Ganetespib, an HSP90 inhibitor, in cancer therapy: From molecular mechanisms to clinical practice. Int. J. Mol. Sci. 2023 24 5 5014 10.3390/ijms24055014 36902446
    [Google Scholar]
  83. Ojha R. Huang H.L. HuangFu W.C. Wu Y.W. Nepali K. Lai M.J. Su C.J. Sung T.Y. Chen Y.L. Pan S.L. Liou J.P. 1-Aroylindoline-hydroxamic acids as anticancer agents, inhibitors of HSP90 and HDAC. Eur. J. Med. Chem. 2018 150 667 677 10.1016/j.ejmech.2018.03.006 29567459
    [Google Scholar]
  84. Ojha R. Nepali K. Chen C.H. Chuang K.H. Wu T.Y. Lin T.E. Hsu K.C. Chao M.W. Lai M.J. Lin M.H. Huang H.L. Chang C.D. Pan S.L. Chen M.C. Liou J.P. Isoindoline scaffold-based dual inhibitors of HDAC6 and HSP90 suppressing the growth of lung cancer in vitro and in vivo. Eur. J. Med. Chem. 2020 190 112086 10.1016/j.ejmech.2020.112086 32058238
    [Google Scholar]
  85. 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 10.1021/acs.jmedchem.0c00491 32320239
    [Google Scholar]
  86. Hauguel C. Ducellier S. Provot O. Ibrahim N. Lamaa D. Balcerowiak C. Letribot B. Nascimento M. Blanchard V. Askenatzis L. Levaique H. Bignon J. Baschieri F. Bauvais C. Bollot G. Renko D. Deroussent A. Prost B. Laisne M.C. Michallet S. Lafanechère L. Papot S. Montagnac G. Tran C. Alami M. Apcher S. Hamze A. Design, synthesis and biological evaluation of quinoline-2-carbonitrile-based hydroxamic acids as dual tubulin polymerization and histone deacetylases inhibitors. Eur. J. Med. Chem. 2022 240 114573 10.1016/j.ejmech.2022.114573 35797900
    [Google Scholar]
  87. Liang X. Tang S. Liu X. Liu Y. Xu Q. Wang X. Saidahmatov A. Li C. Wang J. Zhou Y. Zhang Y. Geng M. Huang M. Liu H. Discovery of novel Pyrrolo[2,3- d ]pyrimidine-based derivatives as potent JAK/HDAC dual inhibitors for the treatment of refractory solid tumors. J. Med. Chem. 2022 65 2 1243 1264 10.1021/acs.jmedchem.0c02111 33586434
    [Google Scholar]
  88. Ren Y. Li S. Zhu R. Wan C. Song D. Zhu J. Cai G. Long S. Kong L. Yu W. Discovery of STAT3 and Histone Deacetylase (HDAC) dual-pathway inhibitors for the treatment of solid cancer. J. Med. Chem. 2021 64 11 7468 7482 10.1021/acs.jmedchem.1c00136 34043359
    [Google Scholar]
  89. Pan T. Dan Y. Guo D. Jiang J. Ran D. Zhang L. Tian B. Yuan J. Yu Y. Gan Z. Discovery of 2,4-pyrimidinediamine derivatives as potent dual inhibitors of ALK and HDAC. Eur. J. Med. Chem. 2021 224 113672 10.1016/j.ejmech.2021.113672 34237620
    [Google Scholar]
  90. Mustafa M. Abd El-Hafeez A.A. Abdelhamid D. Katkar G.D. Mostafa Y.A. Ghosh P. Hayallah A.M. Abuo-Rahma G.E.D.A. A first-in-class anticancer dual HDAC2/FAK inhibitors bearing hydroxamates/benzamides capped by pyridinyl-1,2,4-triazoles. Eur. J. Med. Chem. 2021 222 113569 10.1016/j.ejmech.2021.113569 34111829
    [Google Scholar]
  91. Feng L. Wang G. Chen Y. He G. Liu B. Liu J. Chiang C.M. Ouyang L. Dual-target inhibitors of bromodomain and extra-terminal proteins in cancer: A review from medicinal chemistry perspectives. Med. Res. Rev. 2022 42 2 710 743 10.1002/med.21859 34633088
    [Google Scholar]
  92. He S. Dong G. Li Y. Wu S. Wang W. Sheng C. Potent dual BET/HDAC inhibitors for efficient treatment of pancreatic cancer. Angew. Chem. Int. Ed. 2020 59 8 3028 3032 10.1002/anie.201915896 31943585
    [Google Scholar]
  93. Ghazy E. Zeyen P. Herp D. Hügle M. Schmidtkunz K. Erdmann F. Robaa D. Schmidt M. Morales E.R. Romier C. Günther S. Jung M. Sippl W. Design, synthesis, and biological evaluation of dual targeting inhibitors of histone deacetylase 6/8 and bromodomain BRPF1. Eur. J. Med. Chem. 2020 200 112338 10.1016/j.ejmech.2020.112338 32497960
    [Google Scholar]
  94. Hamdi A. Elhusseiny W.M. Othman D.I.A. Haikal A. Bakheit A.H. El-Azab A.S. Al-Agamy M.H.M. Abdel-Aziz A.A.M. Synthesis, antitumor, and apoptosis-inducing activities of novel 5-arylidenethiazolidine-2,4- dione derivatives: Histone deacetylases inhibitory activity and molecular docking study. Eur. J. Med. Chem. 2022 244 114827 10.1016/j.ejmech.2022.114827 36242988
    [Google Scholar]
  95. Li A. Zheng W. Xiao B. Huang W. Li L. Luo M. Liu Z. Chu B. Jiang Y. Design, synthesis and biological evaluation of pyrimidine base hydroxamic acid derivatives as dual JMJD3 and HDAC inhibitors. Bioorg. Med. Chem. Lett. 2023 94 129466 10.1016/j.bmcl.2023.129466 37660833
    [Google Scholar]
  96. Wang K.L. Yeh T.Y. Hsu P.C. Wong T.H. Liu J.R. Chern J.W. Lin M.H. Yu C.W. Discovery of novel anaplastic lymphoma kinase (ALK) and histone deacetylase (HDAC) dual inhibitors exhibiting antiproliferative activity against non-small cell lung cancer. J. Enzyme Inhib. Med. Chem. 2024 39 1 2318645 10.1080/14756366.2024.2318645 38465731
    [Google Scholar]
  97. Somoza J. R. Skene R. J. Katz B. A. Mol C. Ho J. D. Jennings A. J. Luong C. Arvai A. Buggy J. J. Chi E. Tang J. Sang B. C. Verner E. Wynands R. Leahy E. M. Dougan D. R. Snell G. Navre M. Knuth M. W. Swanson R. V. McRee D. E. Tari L. W. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases Structure 2004 12 7 1325 134
    [Google Scholar]
  98. Fontana A. Cursaro I. Carullo G. Gemma S. Butini S. Campiani G. A therapeutic perspective of hdac8 in different diseases: An overview of selective inhibitors. Int. J. Mol. Sci. 2022 23 17 10014 10.3390/ijms231710014 36077415
    [Google Scholar]
  99. Hassan M.M. Israelian J. Nawar N. Ganda G. Manaswiyoungkul P. Raouf Y.S. Armstrong D. Sedighi A. Olaoye O.O. Erdogan F. Cabral A.D. Angeles F. Altintas R. de Araujo E.D. Gunning P.T. Characterization of conformationally constrained Benzanilide scaffolds for potent and selective HDAC8 targeting. J. Med. Chem. 2020 63 15 8634 8648 10.1021/acs.jmedchem.0c01025 32672458
    [Google Scholar]
  100. Pantelaiou-Prokaki G. Mieczkowska I. Schmidt G.E. Fritzsche S. Prokakis E. Gallwas J. Wegwitz F. HDAC8 suppresses the epithelial phenotype and promotes EMT in chemotherapy-treated basal-like breast cancer. Clin. Epigenetics 2022 14 1 7 10.1186/s13148‑022‑01228‑4 35016723
    [Google Scholar]
  101. Mekala J.R. Ramalingam P.S. Mathavan S. Yamajala R.B.R.D. Moparthi N.R. Kurappalli R.K. Manyam R.R. Synthesis, in vitro and structural aspects of cap substituted Suberoylanilide hydroxamic acid analogs as potential inducers of apoptosis in Glioblastoma cancer cells via HDAC /microRNA regulation. Chem. Biol. Interact. 2022 357 109876 10.1016/j.cbi.2022.109876 35283086
    [Google Scholar]
  102. Moinul M. Amin S.A. Khatun S. Das S. Jha T. Gayen S. A detail survey and analysis of selectivity criteria for indole-based histone deacetylase 8 (HDAC8) inhibitors. J. Mol. Struct. 2022
    [Google Scholar]
  103. Garrido González F.P. Mancilla Percino T. Synthesis, docking study and inhibitory activity of 2,6-diketopiperazines derived from α-amino acids on HDAC8. Bioorg. Chem. 2020 102 104080 10.1016/j.bioorg.2020.104080 32683182
    [Google Scholar]
  104. Darwish S. Ghazy E. Heimburg T. Herp D. Zeyen P. Salem-Altintas R. Ridinger J. Robaa D. Schmidtkunz K. Erdmann F. Schmidt M. Romier C. Jung M. Oehme I. Sippl W. Design, synthesis and biological characterization of Histone Deacetylase 8 (HDAC8) Proteolysis targeting Chimeras (PROTACs) with anti-neuroblastoma activity. Int. J. Mol. Sci. 2022 23 14 7535 10.3390/ijms23147535 35886887
    [Google Scholar]
  105. Sun Z. Deng B. Yang Z. Mai R. Huang J. Ma Z. Chen T. Chen J. Discovery of pomalidomide-based PROTACs for selective degradation of histone deacetylase 8. Eur. J. Med. Chem. 2022 239 114544 10.1016/j.ejmech.2022.114544 35759908
    [Google Scholar]
  106. Huang J. Zhang J. Xu W. Wu Q. Zeng R. Liu Z. Tao W. Chen Q. Wang Y. Zhu W.G. Structure-based discovery of selective Histone Deacetylase 8 degraders with potent anticancer activity. J. Med. Chem. 2023 66 2 1186 1209 10.1021/acs.jmedchem.2c00739 36516047
    [Google Scholar]
  107. Zhao C. Chen D. Suo F. Setroikromo R. Quax W.J. Dekker F.J. Discovery of highly potent HDAC8 PROTACs with anti-tumor activity. Bioorg. Chem. 2023 136 106546 10.1016/j.bioorg.2023.106546 37098288
    [Google Scholar]
  108. Lambona C. Zwergel C. Fioravanti R. Valente S. Mai A. Histone deacetylase 10: A polyamine deacetylase from the crystal structure to the first inhibitors. Curr. Opin. Struct. Biol. 2023 82 102668 10.1016/j.sbi.2023.102668 37542907
    [Google Scholar]
  109. Herbst-Gervasoni C.J. Christianson D.W. X-ray crystallographic snapshots of substrate binding in the active site of Histone Deacetylase 10. Biochemistry 2021 60 4 303 313 10.1021/acs.biochem.0c00936 33449614
    [Google Scholar]
  110. Géraldy M. Morgen M. Sehr P. Steimbach R.R. Moi D. Ridinger J. Oehme I. Witt O. Malz M. Nogueira M.S. Koch O. Gunkel N. Miller A.K. Selective inhibition of Histone Deacetylase 10: Hydrogen bonding to the gatekeeper residue is implicated. J. Med. Chem. 2019 62 9 4426 4443 10.1021/acs.jmedchem.8b01936 30964290
    [Google Scholar]
  111. Herp D. Ridinger J. Robaa D. Shinsky S.A. Schmidtkunz K. Yesiloglu T.Z. Bayer T. Steimbach R.R. Herbst-Gervasoni C.J. Merz A. Romier C. Sehr P. Gunkel N. Miller A.K. Christianson D.W. Oehme I. Sippl W. Jung M. First Fluorescent Acetylspermidine Deacetylation assay for HDAC10 identifies selective inhibitors with cellular target engagement. ChemBioChem 2022 23 14 e202200180 10.1002/cbic.202200180 35608330
    [Google Scholar]
  112. Morgen M. Steimbach R.R. Géraldy M. Hellweg L. Sehr P. Ridinger J. Witt O. Oehme I. Herbst-Gervasoni C.J. Osko J.D. Porter N.J. Christianson D.W. Gunkel N. Miller A.K. Design and synthesis of Dihydroxamic Acids as HDAC6/8/10 inhibitors. ChemMedChem 2020 15 13 1163 1174 10.1002/cmdc.202000149 32348628
    [Google Scholar]
  113. Steimbach R.R. Herbst-Gervasoni C.J. Lechner S. Stewart T.M. Klinke G. Ridinger J. Géraldy M.N.E. Tihanyi G. Foley J.R. Uhrig U. Kuster B. Poschet G. Casero R.A. Jr Médard G. Oehme I. Christianson D.W. Gunkel N. Miller A.K. Aza-SAHA derivatives are selective Histone Deacetylase 10 chemical probes that inhibit Polyamine Deacetylation and phenocopy HDAC10 knockout. J. Am. Chem. Soc. 2022 144 41 18861 18875 10.1021/jacs.2c05030 36200994
    [Google Scholar]
  114. Jiang Q. Tang Y. Hu Q. Wang B. Ruan X. Zhou Q. Discovery of novel itaconimide-based derivatives as potent HDAC inhibitors for the efficient treatment of prostate cancer. Eur. J. Med. Chem. 2024 269 116315 10.1016/j.ejmech.2024.116315 38503167
    [Google Scholar]
  115. Schech A. Kazi A. Yu S. Shah P. Sabnis G. Histone Deacetylase inhibitor entinostat inhibits tumor-initiating cells in triple-negative breast cancer cells. Mol. Cancer Ther. 2015 14 8 1848 1857 10.1158/1535‑7163.MCT‑14‑0778 26037781
    [Google Scholar]
  116. Zhang K. Liu Z. Yao Y. Qiu Y. Li F. Chen D. Hamilton D.J. Li Z. Jiang S. Structure-based design of a selective class I Histone Deacetylase (HDAC) Near-Infrared (NIR) probe for epigenetic regulation detection in triple-negative breast cancer (TNBC). J. Med. Chem. 2021 64 7 4020 4033 10.1021/acs.jmedchem.0c02161 33745280
    [Google Scholar]
  117. Maccallini C. Ammazzalorso A. De Filippis B. Fantacuzzi M. Giampietro L. Amoroso R. HDAC inhibitors for the therapy of triple negative breast cancer. Pharmaceuticals (Basel) 2022 15 6 667 10.3390/ph15060667 35745586
    [Google Scholar]
  118. Bhagat S.D. Chanchal A. Gujrati M. Banerjee A. Mishra R.K. Srivastava A. Implantable HDAC-inhibiting chemotherapeutics derived from hydrophobic amino acids for localized anticancer therapy. Biomater. Sci. 2021 9 1 261 271 10.1039/D0BM01417F 33196720
    [Google Scholar]
  119. Ruzic D. Ellinger B. Djokovic N. Santibanez J.F. Gul S. Beljkas M. Djuric A. Ganesan A. Pavic A. Srdic-Rajic T. Petkovic M. Nikolic K. Discovery of 1-Benzhydryl-Piperazine-based HDAC inhibitors with anti-breast cancer activity: Synthesis, molecular modeling, in vitro and in vivo biological evaluation. Pharmaceutics 2022 14 12 2600 10.3390/pharmaceutics14122600 36559094
    [Google Scholar]
  120. Yao D. Jiang J. Zhang H. Huang Y. Huang J. Wang J. Design, synthesis and biological evaluation of dual mTOR/HDAC6 inhibitors in MDA-MB-231 cells. Bioorg. Med. Chem. Lett. 2021 47 128204 10.1016/j.bmcl.2021.128204 34139324
    [Google Scholar]
  121. Liang T. Hou X. Zhou Y. Yang X. Fang H. Design, synthesis, and biological evaluation of 2,4-Imidazolinedione derivatives as HDAC6 Isoform-selective inhibitors. ACS Med. Chem. Lett. 2019 10 8 1122 1127 10.1021/acsmedchemlett.9b00084 31413795
    [Google Scholar]
  122. Liang T. Xue J. Yao Z. Ye Y. Yang X. Hou X. Fang H. Design, synthesis and biological evaluation of 3, 4-disubstituted-imidazolidine-2, 5-dione derivatives as HDAC6 selective inhibitors. Eur. J. Med. Chem. 2021 221 113526 10.1016/j.ejmech.2021.113526 33992929
    [Google Scholar]
  123. Liang T. Zhou Y. Elhassan R.M. Hou X. Yang X. Fang H. HDAC–Bax multiple ligands enhance Bax-dependent Apoptosis in HeLa cells. J. Med. Chem. 2020 63 20 12083 12099 10.1021/acs.jmedchem.0c01454 33021789
    [Google Scholar]
  124. Khetmalis Y.M. Fathima A. Schweipert M. Debarnot C. Bandaru N.V.M.R. Murugesan S. Jamma T. Meyer-Almes F.J. Sekhar K.V.G.C. Design, synthesis, and biological evaluation of Novel Quinazolin-4(3H)-one-based Histone Deacetylase 6 (HDAC6) inhibitors for anticancer activity. Int. J. Mol. Sci. 2023 24 13 11044 10.3390/ijms241311044 37446224
    [Google Scholar]
  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. 2020 59 50 22494 22499 10.1002/anie.202006725 32780485
    [Google Scholar]
  126. Singh A. Chang T.Y. Kaur N. Hsu K.C. Yen Y. Lin T.E. Lai M.J. Lee S.B. Liou J.P. CAP rigidification of MS-275 and chidamide leads to enhanced antiproliferative effects mediated through HDAC1, 2 and tubulin polymerization inhibition. Eur. J. Med. Chem. 2021 215 113169 10.1016/j.ejmech.2021.113169 33588178
    [Google Scholar]
  127. Ibrahim H.S. Abdelsalam M. Zeyn Y. Zessin M. Mustafa A.H.M. Fischer M.A. Zeyen P. Sun P. Bülbül E.F. Vecchio A. Erdmann F. Schmidt M. Robaa D. Barinka C. Romier C. Schutkowski M. Krämer O.H. Sippl W. Synthesis, molecular docking and biological characterization of Pyrazine Linked 2-Aminobenzamides as new class I selective Histone Deacetylase (HDAC) inhibitors with Anti-Leukemic activity. Int. J. Mol. Sci. 2021 23 1 369 10.3390/ijms23010369 35008795
    [Google Scholar]
  128. Wang Z. Zhao L. Zhang B. Feng J. Wang Y. Zhang B. Jin H. Ding L. Wang N. He S. Discovery of novel polysubstituted N -alkyl acridone analogues as histone deacetylase isoform-selective inhibitors for cancer therapy. J. Enzyme Inhib. Med. Chem. 2023 38 1 2206581 10.1080/14756366.2023.2206581 37144599
    [Google Scholar]
  129. Nepali K. Chang T.Y. Lai M.J. Hsu K.C. Yen Y. Lin T.E. Lee S.B. Liou J.P. Purine/purine isoster based scaffolds as new derivatives of benzamide class of HDAC inhibitors. Eur. J. Med. Chem. 2020 196 112291 10.1016/j.ejmech.2020.112291 32325365
    [Google Scholar]
  130. Singh A. Patel V.K. Jain D.K. Patel P. Rajak H. Panobinostat as pan-deacetylase inhibitor for the treatment of pancreatic cancer: Recent progress and future prospects. Oncol. Ther. 2016 4 1 73 89 10.1007/s40487‑016‑0023‑1 28261641
    [Google Scholar]
  131. Helland Ø. Popa M. Bischof K. Gjertsen B.T. McCormack E. Bjørge L. The HDACi panobinostat shows growth inhibition both in vitro and in a Bioluminescent Orthotopic surgical Xenograft model of ovarian cancer. PLoS One 2016 11 6 e0158208 10.1371/journal.pone.0158208 27352023
    [Google Scholar]
  132. Bots M. Verbrugge I. Martin B.P. Salmon J.M. Ghisi M. Baker A. Stanley K. Shortt J. Ossenkoppele G.J. Zuber J. Rappaport A.R. Atadja P. Lowe S.W. Johnstone R.W. Differentiation therapy for the treatment of t(8;21) acute myeloid leukemia using histone deacetylase inhibitors. Blood 2014 123 9 1341 1352 10.1182/blood‑2013‑03‑488114 24415537
    [Google Scholar]
  133. Li X. Jiang Y. Peterson Y.K. Xu T. Himes R.A. Luo X. Yin G. Inks E.S. Dolloff N. Halene S. Chan S.S.L. Chou C.J. Design of hydrazide-bearing HDACIs based on Panobinostat and their p53 and FLT3-ITD dependency in Antileukemia activity. J. Med. Chem. 2020 63 10 5501 5525 10.1021/acs.jmedchem.0c00442 32321249
    [Google Scholar]
  134. 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 10.1073/pnas.141230798 11438690
    [Google Scholar]
  135. Burslem G.M. Crews C.M. Small-molecule modulation of protein homeostasis. Chem. Rev. 2017 117 17 11269 11301 10.1021/acs.chemrev.7b00077 28777566
    [Google Scholar]
  136. Chen S. Zheng Y. Liang B. Yin Y. Yao J. Wang Q. Liu Y. Neamati N. The application of PROTAC in HDAC. Eur. J. Med. Chem. 2023 260 115746 10.1016/j.ejmech.2023.115746 37607440
    [Google Scholar]
  137. Nalawansha D.A. Crews C.M. PROTACs: An emerging therapeutic modality in precision medicine. Cell Chem. Biol. 2020 27 8 998 1014 10.1016/j.chembiol.2020.07.020 32795419
    [Google Scholar]
  138. Li X. Song Y. Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy. J. Hematol. Oncol. 2020 13 1 50 10.1186/s13045‑020‑00885‑3 32404196
    [Google Scholar]
  139. Gao H. Sun X. Rao Y. PROTAC technology: Opportunities and challenges. ACS Med. Chem. Lett. 2020 11 3 237 240 10.1021/acsmedchemlett.9b00597 32184950
    [Google Scholar]
  140. Qi S.M. Dong J. Xu Z.Y. Cheng X.D. Zhang W.D. Qin J.J. PROTAC: An effective targeted protein degradation strategy for cancer therapy. Front. Pharmacol. 2021 12 692574 10.3389/fphar.2021.692574 34025443
    [Google Scholar]
  141. 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 10.1039/D0CC01485K 32201871
    [Google Scholar]
  142. Smalley J.P. Baker I.M. Pytel W.A. Lin L.Y. Bowman K.J. Schwabe J.W.R. Cowley S.M. Hodgkinson J.T. Optimization of class I Histone Deacetylase PROTACs reveals that HDAC1/2 degradation is critical to induce apoptosis and cell arrest in cancer cells. J. Med. Chem. 2022 65 7 5642 5659 10.1021/acs.jmedchem.1c02179 35293758
    [Google Scholar]
  143. 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 10.1039/D0CC03243C 32840532
    [Google Scholar]
  144. Xiao Y. Hale S. Awasthee N. Meng C. Zhang X. Liu Y. Ding H. Huo Z. Lv D. Zhang W. He M. Zheng G. Liao D. HDAC3 and HDAC8 PROTAC dual degrader reveals roles of histone acetylation in gene regulation. Cell Chem. Biol. 2023 30 11 1421 1435.e12 10.1016/j.chembiol.2023.07.010 37572669
    [Google Scholar]
  145. Jia Q. Zhang Y. Liu F. Dong W. Zhu L. Wang F. Jiang J.H. Cell-specific degradation of Histone Deacetylase using warhead-caged proteolysis targeting chimeras. Anal. Chem. 2023 95 45 16474 16480 10.1021/acs.analchem.3c01236 37903331
    [Google Scholar]
  146. Li Y. Seto E. HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harb. Perspect. Med. 2016 6 10 a026831 10.1101/cshperspect.a026831 27599530
    [Google Scholar]
  147. Vong P. Ouled-Haddou H. Garçon L. Histone Deacetylases function in the control of early Hematopoiesis and Erythropoiesis. Int. J. Mol. Sci. 2022 23 17 9790 10.3390/ijms23179790 36077192
    [Google Scholar]
  148. Ding P. Ma Z. Liu D. Pan M. Li H. Feng Y. Zhang Y. Shao C. Jiang M. Lu D. Han J. Wang J. Yan X. Lysine acetylation/deacetylation modification of immune-related molecules in cancer immunotherapy. Front. Immunol. 2022 13 865975 10.3389/fimmu.2022.865975 35585975
    [Google Scholar]
  149. Tavares M.T. Kozikowski A.P. Shen S. Mercaptoacetamide: A promising zinc-binding group for the discovery of selective histone deacetylase 6 inhibitors. Eur. J. Med. Chem. 2021 209 112887 10.1016/j.ejmech.2020.112887 33035922
    [Google Scholar]
  150. Halsall J.A. Turner B.M. Histone deacetylase inhibitors for cancer therapy: An evolutionarily ancient resistance response may explain their limited success. BioEssays 2016 38 11 1102 1110 10.1002/bies.201600070 27717012
    [Google Scholar]
  151. Ferro A. Pantazaka E. Athanassopoulos C.M. Cuendet M. Histone deacetylase-based dual targeted inhibition in multiple myeloma. Med. Res. Rev. 2023 43 6 2177 2236 10.1002/med.21972 37191917
    [Google Scholar]
  152. Shen L. Li Y. Li N. Shen L. Li Z. Comprehensive analyses reveal the role of histone deacetylase genes in prognosis and immune response in low-grade glioma. PLoS One 2022 17 10 e0276120 10.1371/journal.pone.0276120 36227941
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673332285241104091609
Loading
Structural Modifications and Prospects of Histone Deacetylase (HDAC) Inhibitors in Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0109298673332285241104091609
/content/journals/cmc/10.2174/0109298673332285241104091609
/content/journals/cmc/10.2174/0109298673332285241104091609
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: clinical research ; cancer ; HDAC8 ; HDAC10 ; PROTAC ; HDACis ; dual target inhibitors

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test