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选择性组蛋白去乙酰化酶抑制剂的研究进展
Progress in the Research of Selective Histone deacetylase Inhibitors

DOI: 10.12677/AMC.2021.91002, PP. 9-23

Keywords: 组蛋白去乙酰化酶,选择性抑制剂,潜在适应症
Histone deacetylase
, Selective Inhibitors, Potential Indications

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Abstract:

组蛋白去乙酰化酶(HDACs)参与组蛋白和非组蛋白赖氨酸残基乙酰化和去乙酰化动态平衡过程的调节,它的异常表达与癌症、神经性疾病、炎症、代谢异常等一系列疾病相关。HDAC具有多种亚型,且组织分布及生理功能均有差异,开发亚型选择性HDAC抑制剂可降低其毒副作用,并成为近年来的研究热点,目前已报道多种类型的选择性HDAC抑制剂。本文综述了现阶段选择性HDAC抑制剂的研究进展和潜在适应症。
Histone deacetylases (HDACs) play a crucial role in regulating the balance of acetylation and deacetylation of lysine residues of histones and non-histone proteins, whose overexpression is closely associated with a great variety of cancers, neurological diseases, inflammatory diseases, metabolic disorders and so on. HDAC has lots of subtypes, and the tissue distribution and physiological functions are different, the development of subtype selective HDAC inhibitors can reduce its toxic and side effects, and has become a research hotspot in recent years. Several HDAC inhibitors have been reported so far. This review summarizes the current research progress and potential indications of selective HDAC inhibitors.

References

[1]  Zhao, C., Dong, H., Xu, Q., et al. (2020) Histone Deacetylase (HDAC) Inhibitors in Cancer: A Patent Review (2017-Present). Expert Opinion on Therapeutic Patents, 30, 263-274.
https://doi.org/10.1080/13543776.2020.1725470
[2]  Sultana, F., Manasa, K.L., Shaik, S.P., et al. (2019) Zinc Dependent Histone Deacetylase Inhibitors in Cancer Therapeutics: Recent Update. Current Medicinal Chemistry, 26, 7212-7280.
https://doi.org/10.2174/0929867325666180530094120
[3]  Zhang, H., Shang, Y.P., Chen, H.Y., et al. (2017) Histone Deacetylase Function as Novel Potential Therapeutic Targets for Cancer. Hepatology Research, 47, 149-159.
https://doi.org/10.1111/hepr.12757
[4]  Zhao, C., Zang, J., Ding, Q., et al. (2018) Discovery of Meta-Sulfamoyl N-Hydroxybenzamides as HDAC8 Selective Inhibitors. European Journal of Medicinal Chemistry, 150, 282-291.
https://doi.org/10.1016/j.ejmech.2018.03.002
[5]  Parra, M. (2015) Class IIa HDACs—New Insights into Their Functions in Physiology and Pathology. The FEBS Journal, 282, 1736-1744.
https://doi.org/10.1111/febs.13061
[6]  Li, T., Zhang, C., Hassan, S., et al. (2018) Histone Deacetylase 6 in Cancer. Journal of Hematology & Oncology, 11, 111.
https://doi.org/10.1186/s13045-018-0654-9
[7]  Yue, L., Sharma, V., Horvat, N.P., et al. (2020) HDAC11 Deficiency Disrupts Oncogene-Induced Hematopoiesis in Myeloproliferative Neoplasms. Blood, 135, 191-207.
https://doi.org/10.1182/blood.2019895326
[8]  Thomas, A.M., David, J.W. and Sandro, B. (2003) Histone Deacetylase Inhibitors. Journal of Medicinal Chemistry, 46, 5097-5116.
https://doi.org/10.1021/jm0303094
[9]  Marson, C.M. (2009) Histone Deacetylase Inhibitors: Design, Structure-Activity Relationships and Therapeutic Implications for Cancer. Anti-Cancer Agents in Medicinal Chemistry, 9, 661-692.
https://doi.org/10.2174/187152009788679976
[10]  Luan, Y., Li, J., Bernatchez, J.A., et al. (2019) Kinase and Histone Deacetylase Hybrid Inhibitors for Cancer Therapy. Journal of Medicinal Chemistry, 62, 3171-3183.
https://doi.org/10.1021/acs.jmedchem.8b00189
[11]  Hess-Stumpp, H. (2005) Histone Deacetylase Inhibitors and Cancer: From Cell Biology to the Clinic. European Journal of Cell Biology, 84, 109-121.
https://doi.org/10.1016/j.ejcb.2004.12.010
[12]  Trapani, D., Esposito, A., Criscitiello, C., et al. (2017) Entinostat for the Treatment of Breast Cancer. Expert Opinion on Investigational Drugs, 26, 965-971.
https://doi.org/10.1080/13543784.2017.1353077
[13]  Fournel, M., Bonfils, C., Hou, Y., et al. (2008) MGCD0103, a Novel Isotype-Selective Histone Deacetylase Inhibitor, Has Broad Spectrum Antitumor Activity in Vitro and in Vivo. Molecular Cancer Therapeutics, 7, 759-768.
https://doi.org/10.1158/1535-7163.MCT-07-2026
[14]  Graziano, M.J., Spoon, T.A., Cockrell, E.A., et al. (2001) Induction of Apoptosis in Rat Peripheral Blood Lymphocytes by the Anticancer Drug CI-994 (Acetyldinaline). Journal of Biomedicine and Biotechnology, 1, 52-61.
https://doi.org/10.1155/S1110724301000146
[15]  Beckers, T., Burkhardt, C., Wieland, H., et al. (2007) Distinct Pharmacological Properties of Second Generation HDAC Inhibitors with the Benzamide or Hydroxamate Head Group. International Journal of Cancer, 121, 1138-1148.
https://doi.org/10.1002/ijc.22751
[16]  Henning, S.W. (2010) 178 Preclinical Characterization of 4SC-202, a Novel Isotype Specific HDAC Inhibitor. European Journal of Cancer—Supplement, 8, 61.
https://doi.org/10.1016/S1359-6349(10)71883-8
[17]  Peng, X., Liao, G., Sun, P., et al. (2019) An Overview of HDAC Inhibitors and Their Synthetic Routes. Current Topics in Medicinal Chemistry, 19, 1005-1040.
https://doi.org/10.2174/1568026619666190227221507
[18]  Ralph, M. (2015) Inhibitors of Histone Deacetylase. PCT International Application, 2015069693, May 14.
[19]  Tang, S., Cheng, B., Zhe, N., et al. (2018) Histone Deacetylase Inhibitor BG45-Mediated HO-1 Expression Induces Apoptosis of Multiple Myeloma Cells by the JAK2/STAT3 Pathway. Anticancer Drugs, 29, 61-74.
https://doi.org/10.1097/CAD.0000000000000568
[20]  Malvaez, M., McQuown, S.C., Rogge, G.A., et al. (2013) HDAC3-Selective Inhibitor Enhances Extinction of Cocaine- Seeking Behavior in a Persistent Manner. Proceedings of the National Academy of Sciences of the United States of America, 110, 2647-2652.
https://doi.org/10.1073/pnas.1213364110
[21]  Zhang, M.J., Zhao, Q.C., Xia, M.X., et al. (2020) The HDAC3 Inhibitor RGFP966 Ameliorated Ischemic Brain Damage by Downregulating the AIM2 Inflammasome. The FASEB Journal, 34, 648-662.
https://doi.org/10.1096/fj.201900394RRR
[22]  Wagner, F.F., Lundh, M., Kaya, T., et al. (2016) An Isochemogenic Set of Inhibitors to Define the Therapeutic Potential of Histone Deacetylases in β-Cell Protection. ACS Chemical Biology, 11, 363-374.
https://doi.org/10.1021/acschembio.5b00640
[23]  Wagner, F.F., Zhang, Y.L., Fass, D.M., et al. (2015) Kinetically Selective Inhibitors of Histone Deacetylase 2 (HDAC2) as Cognition Enhancers. Chemical Science, 6, 804-815.
https://doi.org/10.1039/C4SC02130D
[24]  Hirata, Y., Sasaki, T., Kanki, H., et al. (2018) New 5-Aryl-Substituted 2-Aminobenzamide-Type HDAC Inhibitors with a Diketopiperazine Group and Their Ameliorating Effects on Ischemia-Induced Neuronal Cell Death. Scientific Reports, 8, Article No. 1400.
https://doi.org/10.1038/s41598-018-19664-9
[25]  Mendoza-Sanchez, R., Cotnoir-White, D., Kulpa, J., et al. (2015) Design, Synthesis and Evaluation of Antiestrogen and Histone Deacetylase Inhibitor Molecular Hybrids. Bioorganic & Medicinal Chemistry, 23, 7597-7606.
https://doi.org/10.1016/j.bmc.2015.11.005
[26]  Boissinot, M., Inman, M., Hempshall, A., et al. (2012) Induction of Differentiation and Apoptosis in Leukaemic Cell Lines by the Novel Benzamide Family Histone Deacetylase 2 and 3 Inhibitor MI-192. Leukemia Research, 36, 1304-1310.
https://doi.org/10.1016/j.leukres.2012.07.002
[27]  Eyre, T.A., Collins, G.P., Gupta, A., et al. (2019) A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of CXD101 in Patients with Advanced Cancer. Cancer, 125, 99-108.
https://doi.org/10.1002/cncr.31791
[28]  Poli, G., Di Fabio, R., Ferrante, L., et al. (2017) Largazole Analogues as Histone Deacetylase Inhibitors and Anticancer Agents: An Overview of Structure-Activity Relationships. ChemMedChem, 12, 1917-1926.
https://doi.org/10.1002/cmdc.201700563
[29]  Ma, N., Luo, Y., Wang, Y., et al. (2016) Selective Histone Deacetylase Inhibitors with Anticancer Activity. Current Topics in Medicinal Chemistry, 16, 415-426.
https://doi.org/10.2174/1568026615666150813145629
[30]  Parlet, C.P., Kavanaugh, J.S., Crosby, H.A., et al. (2019) Apicidin Attenuates MRSA Virulence through Quorum-Sensing Inhibition and Enhanced Host Defense. Cell Reports, 27, 187-198.e6.
https://doi.org/10.1016/j.celrep.2019.03.018
[31]  Arts, J., King, P., Mari?n, A., et al. (2009) JNJ-26481585, a Novel “Second-Generation” Oral Histone Deacetylase Inhibitor, Shows Broad-Spectrum Preclinical Antitumoral Activity. Clinical Cancer Research, 15, 6841-6851.
https://doi.org/10.1158/1078-0432.CCR-09-0547
[32]  Su, G.H., Sohn, T.A., Ryu, B., et al. (2000) A Novel Histone Deacetylase Inhibitor Identified by High-Throughput Transcriptional Screening of a Compound Library. Cancer Research, 60, 3137-3142.
[33]  Sharma, V., Koul, N., Joseph, C., et al. (2010) HDAC Inhibitor, Scriptaid, Induces Glioma Cell Apoptosis through JNK Activation and Inhibits Telomerase Activity. Journal of Cellular and Molecular Medicine, 14, 2151-2161.
https://doi.org/10.1111/j.1582-4934.2009.00844.x
[34]  Wood, T.E., Dalili, S., Simpson, C.D., et al. (2010) Selective Inhibition of Histone Deacetylases Sensitizes Malignant Cells to Death Receptor Ligands. Molecular Cancer Therapeutics, 9, 246-256.
https://doi.org/10.1158/1535-7163.MCT-09-0495
[35]  McCourt, C., Maxwell, P., Mazzucchelli, R., et al. (2012) Elevation of c-FLIP in Castrate-Resistant Prostate Cancer Antagonizes Therapeutic Response to Androgen Receptor-Targeted Therapy. Clinical Cancer Research, 18, 3822-3833.
https://doi.org/10.1158/1078-0432.CCR-11-3277
[36]  Balasubramanian, S., Ramos, J., Luo, W., et al. (2008) A Novel Histone Deacetylase 8 (HDAC8)-Specific Inhibitor PCI-34051 Induces Apoptosis in T-Cell Lymphomas. Leukemia, 22, 1026-1034.
https://doi.org/10.1038/leu.2008.9
[37]  Suzuki, T., Muto, N., Bando, M., et al. (2014) Design, Synthesis, and Biological Activity of NCC149 Derivatives as Histone Deacetylase 8-Selective Inhibitors. ChemMedChem, 9, 657-664.
https://doi.org/10.1002/cmdc.201300414
[38]  Tng, J., Lim, J., Wu, K.C., et al. (2020) Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class I HDAC Enzymes and Cancer Cell Proliferation. Journal of Medicinal Chemistry, 63, 5956-5971.
https://doi.org/10.1021/acs.jmedchem.0c00230
[39]  Hassan, M.M., Israelian, J., Nawar, N., et al. (2020) Characterization of Conformationally Constrained Benzanilide Scaffolds for Potent and Selective HDAC8 Targeting. Journal of Medicinal Chemistry, 63, 8634-8648.
https://doi.org/10.1021/acs.jmedchem.0c01025
[40]  Yang, Y.C., Chen, C.N., Wu, C.I., et al. (2013) NBM-T-L-BMX-OS01, Semisynthesized from Osthole, Is a Novel Inhibitor of Histone Deacetylase and Enhances Learning and Memory in Rats. Evidence-Based Complementary and Alternative Medicine, 2013, Article ID: 514908.
https://doi.org/10.1155/2013/514908
[41]  Moffat, D., Patel, S., Day, F., et al. (2010) Discovery of 2-(6-{[(6-fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex- 3-yl)-N-hydroxypyrim Idine-5-carboxamide (CHR-3996), a Class I Selective Orally Active Histone Deacetylase Inhibitor. Journal of Medicinal Chemistry, 53, 8663-8678.
https://doi.org/10.1021/jm101177s
[42]  Marek, L., Hamacher, A., Hansen, F.K., et al. (2013) Histone Deacetylase (HDAC) Inhibitors with a Novel Connecting Unit Linker Region Reveal a Selectivity Profile for HDAC4 and HDAC5 with Improved Activity against Chemoresistant Cancer Cells. Journal of Medicinal Chemistry, 56, 427-436.
https://doi.org/10.1021/jm301254q
[43]  Di Giorgio, E., Gagliostro, E. and Brancolini, C. (2015) Selective Class IIa HDAC Inhibitors: Myth or Reality. Cellular and Molecular Life Sciences, 72, 73-86.
https://doi.org/10.1007/s00018-014-1727-8
[44]  Olsson, A., Bj?rk, A., Vallon-Christersson, J., et al. (2010) Tasquinimod (ABR-215050), a Quinoline-3-Carboxamide Anti-Angiogenic Agent, Modulates the Expression of Thrombospondin-1 in Human Prostate Tumors. Molecular Cancer, 9, 107.
https://doi.org/10.1186/1476-4598-9-107
[45]  Mai, A., Massa, S., Pezzi, R., et al. (2005) Class II (IIa)-Selective Histone Deacetylase Inhibitors. 1. Synthesis and Biological Evaluation of Novel (Aryloxopropenyl)pyrrolyl Hydroxyamides. Journal of Medicinal Chemistry, 48, 3344-3353.
https://doi.org/10.1021/jm049002a
[46]  Butler, K.V., Kalin, J., Brochier, C., et al. (2010) Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A. Journal of the American Chemical Society, 132, 10842-10846.
https://doi.org/10.1021/ja102758v
[47]  Haggarty, S.J., Koeller, K.M., Wong, J.C., et al. (2003) Domain-Selective Small-Molecule Inhibitor of Histone Deacetylase 6 (HDAC6)-Mediated Tubulin Deacetylation. Proceedings of the National Academy of Sciences of the United States of America, 100, 4389-4394.
https://doi.org/10.1073/pnas.0430973100
[48]  Tan, J., Cang, S., Ma, Y., et al. (2010) Novel Histone Deacetylase Inhibitors in Clinical Trials as Anti-Cancer Agents. Journal of Hematology & Oncology, 3, 5.
https://doi.org/10.1186/1756-8722-3-5
[49]  Jochems, J., Boulden, J., Lee, B.G., et al. (2014) Antidepressant-Like Properties of Novel HDAC6-Selective Inhibitors with Improved Brain Bioavailability. Neuropsychopharmacology, 39, 389-400.
https://doi.org/10.1038/npp.2013.207
[50]  Kozikowski, A.P., Tapadar, S., Luchini, D.N., et al. (2008) Use of the Nitrile Oxide Cycloaddition (NOC) Reaction for Molecular Probe Generation: A New Class of Enzyme Selective Histone Deacetylase Inhibitors (HDACIs) Showing Picomolar Activity at HDAC6. Journal of Medicinal Chemistry, 51, 4370-4373.
https://doi.org/10.1021/jm8002894
[51]  Lee, J.H., Mahendran, A., Yao, Y., et al. (2013) Development of a Histone Deacetylase 6 Inhibitor and Its Biological Effects. Proceedings of the National Academy of Sciences of the United States of America, 110, 15704-15709.
https://doi.org/10.1073/pnas.1313893110
[52]  Bergman, J.A., Woan, K., Perez-Villarroel, P., et al. (2012) Selective Histone Deacetylase 6 Inhibitors Bearing Substituted Urea Linkers Inhibit Melanoma Cell Growth. Journal of Medicinal Chemistry, 55, 9891-9899.
https://doi.org/10.1021/jm301098e
[53]  Hideshima, T., Qi, J., Paranal, R.M., et al. (2016) Discovery of Selective Small-Molecule HDAC6 Inhibitor for Overcoming Proteasome Inhibitor Resistance in Multiple Myeloma. Proceedings of the National Academy of Sciences of the United States of America, 113, 13162-13167.
https://doi.org/10.1073/pnas.1608067113
[54]  Inks, E.S., Josey, B.J., Jesinkey, S.R., et al. (2012) A Novel Class of Small Molecule Inhibitors of HDAC6. ACS Chemical Biology, 7, 331-339.
https://doi.org/10.1021/cb200134p
[55]  Wagner, F.F., Olson, D.E., Gale, J.P., et al. (2013) Potent and Selective Inhibition of Histone Deacetylase 6 (HDAC6) Does Not Require a Surface-Binding Motif. Journal of Medicinal Chemistry, 56, 1772-1776.
https://doi.org/10.1021/jm301355j
[56]  Kozikowski, A.P., Shen, S., Pardo, M., et al. (2019) Brain Penetrable Histone Deacetylase 6 Inhibitor SW-100 Ameliorates Memory and Learning Impairments in a Mouse Model of Fragile X Syndrome. ACS Chemical Neuroscience, 10, 1679-1695.
https://doi.org/10.1021/acschemneuro.8b00600
[57]  Shen, S., Hadley, M., Ustinova, K., et al. (2019) Discovery of a New Isoxazole-3-hydroxamate-Based Histone Deacetylase 6 Inhibitor SS-208 with Antitumor Activity in Syngeneic Melanoma Mouse Models. Journal of Medicinal Chemistry, 62, 8557-8577.
https://doi.org/10.1021/acs.jmedchem.9b00946
[58]  Vergani, B., Sandrone, G., Marchini, M., et al. (2019) Novel Benzohydroxamate-Based Potent and Selective Histone Deacetylase 6 (HDAC6) Inhibitors Bearing a Pentaheterocyclic Scaffold: Design, Synthesis, and Biological Evaluation. Journal of Medicinal Chemistry, 62, 10711-10739.
https://doi.org/10.1021/acs.jmedchem.9b01194
[59]  Martin, M.W., Lee, J.Y., Lancia, D.R., et al. (2018) Discovery of Novel N-Hydroxy-2-Arylisoindoline-4-Carbox- amides as Potent and Selective Inhibitors of HDAC11. Bioorganic & Medicinal Chemistry Letters, 28, 2143-2147.
https://doi.org/10.1016/j.bmcl.2018.05.021
[60]  Son, S.I., Cao, J., Zhu, C.L., et al. (2019) Activity-Guided Design of HDAC11-Specific Inhibitors. ACS Chemical Biology, 14, 1393-1397.
https://doi.org/10.1021/acschembio.9b00292

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