|
|
组蛋白去乙酰化酶抑制剂的研究进展
|
Abstract:
组蛋白去乙酰化酶于上世纪90年代发现，其在氨基酸侧链的翻译后修饰起到重要作用，并且广泛在肿瘤细胞中高度表达。因此，研究开发新型的组蛋白去乙酰化酶抑制剂可以有效靶向针对肿瘤细胞。30多年来，人们对组蛋白去乙酰化酶的认识愈加清晰，并在这些认识的基础上创造了许多针对不同癌症的小分子药物。本文综述了目前临床上对组蛋白去乙酰化酶抑制剂的研究，并分类介绍其研究进展，希望能对后续组蛋白去乙酰化酶的抑制剂开发有所帮助。
Histone deacetylase was discovered in the 90s of last century which plays an important role in the post-translational modification of side chains, and was widely expressed in tumor cells. Therefore, researching and developing novel histone deacetylase inhibitors can effectively target tumor cells. Over the past 30 years, people’s understanding of histone deacetylase had become increasingly clear, and many small molecule drugs for different cancers was created on the basis of these understandings. This article reviews the current clinical research on histone deacetylase inhibitors and categorizes their progress, hoping to be helpful for the subsequent development of histone deacetylase inhibitors.
| [1] | Azevedo, C. and Saiardi A. (2016) Why Always Lysine? The Ongoing Tale of One of the Most Modified Amino Acids. Advances in Biological Regulation, 60, 144-150. https://doi.org/10.1016/j.jbior.2015.09.008 |
| [2] | Xu, H., Zhou, J. and Lin, S. (2017) PLMD: An Updated Data Resource of Protein Lysine Modifications. Journal of Genetics and Ge-nomics, 44, 243-250. https://doi.org/10.1016/j.jgg.2017.03.007 |
| [3] | Ganesan, A. (2018) Epigenetic Drug Discov-ery: A Success Story for Cofactor Interference. Philosophical Transactions of the Royal Society B: Biological Sciences, 373, Article ID: 20170069. https://doi.org/10.1098/rstb.2017.0069 |
| [4] | Yoshida, M., Kudo, N. and Kosono, S. (2017) Chemical and Structural Biology of Protein Lysine Deacetylases. Proceedings of the Japan Academy, Series B, 93, 297-321. https://doi.org/10.2183/pjab.93.019 |
| [5] | Jiang, Y., Liu, J. and Chen, D. (2017) Sirtuin Inhibition: Strate-gies, Inhibitors and Therapeutic Potential. Trends in Pharmacological Sciences, 38, 459-472. https://doi.org/10.1016/j.tips.2017.01.009 |
| [6] | Yoshida, M., Kijima, M. and Akita, M. (1990) Potent and Specific Inhibition of Mammalian Histone Deacetylase both in Vivo and in Vitro by Trichostatina. Journal of Biological Chemistry, 265, 17174-17179.
https://doi.org/10.1016/S0021-9258(17)44885-X |
| [7] | Ganesan, A. (2016) Romidepsin and the Zinc-Binding Thiol Family of Natural Product HDAC Inhibitors. In: Fischer, J. and Childers, W.E., Eds., Successful Drug Discovery, Wiley, Hoboken, 13-29.
https://doi.org/10.1002/9783527800315.ch2 |
| [8] | Jing, Q., Hu, X., Ma, Y., et al. (2019) Marine-Derived Natural Lead Compound Disulfide-Linked Dimer Psammaplin A: Biological Activity and Structural Modification. Marine Drugs, 17, Article 384.
https://doi.org/10.3390/md17070384 |
| [9] | Wen, S., Carey, K.L., Nakao, Y., Fusetani, N., Packham, G. and Gane-san, A. (2007) Total Synthesis of Azumamide A and Azumamide E, Evaluation as Histone Deacetylase Inhibitors and Design of a More Potent Analogue. Organic Letters, 9, 1105-1108. https://doi.org/10.1021/ol070046y |
| [10] | Wang, Y. and Wang, H. (2022) The Emerging Role of Histone Deacetylase 1 in Allergic Diseases. Frontiers in Immunology, 13, Article 1027403. https://doi.org/10.3389/fimmu.2022.1027403 |
| [11] | Roizman, B. (2011) The Checkpoints of Viral Gene Expression in Productive and Latent Infection: The Role of the HDAC/CoREST/LSD1/REST Repressor Complex. Journal of Virology, 85, 7474-7482.
https://doi.org/10.1128/JVI.00180-11 |
| [12] | Zhang, H., Ji, L., Yang, Y., Zhang, X., Gang, Y. and Bai, L. (2020) The Role of HDACs and HDACi in Cartilage and Osteoarthritis. Frontiers in Cell and Developmental Biology, 8, Article 560117.
https://doi.org/10.3389/fcell.2020.560117 |
| [13] | We？wer, M., Lewis, M.C., Wagner, F.F. and Holson, E.B. (2013) Therapeutic Potential of Isoform Selective HDAC Inhibitors for the Treatment of Schizophrenia. Future Medicinal Chemistry, 5, 1491-1508.
https://doi.org/10.4155/fmc.13.141 |
| [14] | Kim, J.Y., Cho, H., Yoo, J., et al. (2022) Pathological Role of HDAC8: Cancer and Beyond. Cells, 11, Article 3161.
https://doi.org/10.3390/cells11193161 |
| [15] | Fontana, A., Cursaro, I., Carullo, G., Gemma, S., Butini, S. and Cam-piani, G. (2022) A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors. In-ternational Journal of Molecular Sciences, 23, Article 10014. https://doi.org/10.3390/ijms231710014 |
| [16] | Wu, Y., Hou, F., Wang, X., Kong, Q., Han, X. and Bai, B. (2016) Aberrant Expression of Histone Deacetylases 4 in Cognitive Disorders: Molecular Mechanisms and a Potential Target. Frontiers in Molecular Neuroscience, 9, Article 00114. https://doi.org/10.3389/fnmol.2016.00114 |
| [17] | Mielcarek, M., zielonka, D., Carnemolla, A., et al. (2015) HDAC4 as a Potential Therapeutic Target in Neurodegenerative Diseases: A Summary of Recent Achievements. Frontiers in Cel-lular Neuroscience, 9, Article 00042.
https://doi.org/10.3389/fncel.2015.00042 |
| [18] | Mathias, R.A., Guise, A.J. and Cristea, I.M. (2015) Post-Translational Modifications Regulate Class IIa Histone Deacetylase (HDAC) Function in Health and Disease. Mo-lecular & Cellular Proteomics, 14, 456-470.
https://doi.org/10.1074/mcp.O114.046565 |
| [19] | Wang, Y., Abrol, R., Mak, J.Y.W., et al. (2022) Histone Deacety-lase 7: A Signalling Hub Controlling Development, Inflammation, Metabolism and Disease. The FEBS Journal, Article ID: 16437. https://doi.org/10.1111/febs.16437 |
| [20] | Hu, S., Cho, E.-H. and Lee, J.-Y. (2020) Histone Deacetylase 9: Its Role in the Pathogenesis of Diabetes and Other Chronic Diseases. Diabetes & Metabolism Journal, 44, 234-244. https://doi.org/10.4093/dmj.2019.0243 |
| [21] | Seidel, C., Schnekenburger, M., Dicato, M. and Diederich, M. (2015) Histone Deacetylase 6 in Health and Disease. Epigenomics, 7, 103-118. https://doi.org/10.2217/epi.14.69 |
| [22] | Pulya, S., Amin, S.A. and Adhikari, N. (2021) HDAC6 as Privileged Target in Drug Discovery: A Perspective. Pharmacological Research, 163, Article ID: 105274. https://doi.org/10.1016/j.phrs.2020.105274 |
| [23] | Cheng, F., Zheng, B., Wang, J., et al. (2021) Histone Deacetylase 10, a Potential Epigenetic Target for therapy. Bioscience Reports, 41. https://doi.org/10.1042/BSR20210462 |
| [24] | Liu, S.S., Wu, F. and Jin, Y.M. (2020) HDAC11: A Rising Star in Epigenetics. Biomedicine & Pharmacotherapy, 131, Article ID: 110607. https://doi.org/10.1016/j.biopha.2020.110607 |
| [25] | Chen, H., Xie, C., Chen, Q. and Zhuang, S. (2022) HDAC11, an Emerging Therapeutic Target for Metabolic Disorders. Frontiers in Endocrinology, 13, Article 989305. https://doi.org/10.3389/fendo.2022.989305 |
| [26] | Marks, P.A. and Breslow, R. (2007) Dimethyl Sulfoxide to Vori-nostat: Development of this Histone Deacetylase Inhibitor as an Anticancer Drug. Nature Biotechnology, 25, 84-90. https://doi.org/10.1038/nbt1272 |
| [27] | Ossenkoppele, G.J., Lowenberg, B., Zachee, P., et al. (2013) A Phase I First-in-Human Study with Tefinostat—A Monocyte/Macrophage Targeted Histone Deacetylase Inhibitor—In Patients with Advanced Haematological Malignancies. British Journal of Haematology, 162, 191-201. https://doi.org/10.1111/bjh.12359 |
| [28] | Jung, D.E., Park, S.B., Kim, K., Kim, C. and Song, S.Y. (2017) CG200745, an HDAC Inhibitor, Induces Anti-Tumour Effects in Cholangiocarcinoma Cell Lines via miRNAs Targeting the Hippo Pathway. Scientific Reports, 7, Article No. 10921. https://doi.org/10.1038/s41598-017-11094-3 |
| [29] | Santo, L., Hideshima, T., Kung, A.L., et al. (2012) Preclinical Activity, Pharmacodynamic, and Pharmacokinetic Properties of a Se-lective HDAC6 Inhibitor, ACY-1215, in Combination with Bortezomib in Multiple Myeloma. Blood, 119, 2579-2589. https://doi.org/10.1182/blood-2011-10-387365 |
| [30] | Huang, P., Almeciga-Pinto, I., Jarpe, M., et al. (2017) Selec-tive HDAC Inhibition by ACY-241 Enhances the Activity of Paclitaxel in Solid Tumor Models. Oncotarget, 8, 2694-2707. https://doi.org/10.18632/oncotarget.13738 |
| [31] | Cai, X., Zhai, H.X., Wang, J., et al. (2010) Discovery of 7-(4-(3-Ethynylphenylamino)-7-Methoxyquinazolin- 6-Yloxy)-N-Hydroxyheptanamide (CUDC-101) as a Potent Multi-Acting HDAC, EGFR and HER2 Inhibitor for the Treatment of Cancer. Journal of Medicinal Chemistry, 53, 2000-2009. https://doi.org/10.1021/jm901453q |
| [32] | Mehrling, T. and Chen, Y. (2015) The Alkylating-HDAC In-hibition Fusion Principle: Taking Chemotherapy to the Next Level with the First in Class Molecule EDO-S101. An-ti-Cancer Agents in Medicinal Chemistry, 16, 20-28.
https://doi.org/10.2174/1871520615666150518092027 |
| [33] | Finn, P.W., Loza, E. and Carstensen, E. (2016) The Discovery and Development of Belinostat. In: Fischer, J. and Childers, W.E., Eds., Successful Drug Discovery, Wiley, Hoboken, 31-57. https://doi.org/10.1002/9783527800315.ch3 |
| [34] | Atadja, P. and Perez, L. (2016) Discovery and Development of Farydak (NVP-LBH589, Panobinostat) as an Anticancer Drug. In: Fischer, J. and Childers, W.E., Eds., Successful Drug Discovery, Wiley, Hoboken, 59-88.
https://doi.org/10.1002/9783527800315.ch4 |
| [35] | Wang, H., Yu, N., Chen, D., et al. (2011) Discovery of (2E)-3-{2-Butyl-1-[2-(Diethylamino)Ethyl]-1H-Benzimidazol- 5-yl}-N-Hydroxyacrylamide (SB939), an Orally Active Histone Deacetylase Inhibitor with a Superior Preclinical Profile. Journal of Medicinal Chemistry, 54, 4694-4720. https://doi.org/10.1021/jm2003552 |
| [36] | Matalon, S., Palmer, B.E., Nold, M.F., et al. (2010) The Histone Deacety-lase Inhibitor ITF2357 Decreases Surface CXCR4 and CCR5 Expression on CD4+ T-Cells and Monocytes and is Supe-rior to Valproic Acid for Latent HIV-1 Expression in Vitro. JAIDS: Journal of Acquired Immune Deficiency Syndromes, 54, 1-9.
https://doi.org/10.1097/QAI.0b013e3181d3dca3 |
| [37] | Buggy, J.J., Cao, Z.A., Bass, K.E., et al. (2006) CRA-024781: A Novel Synthetic Inhibitor of Histone Deacetylase Enzymes with Antitumor Activity in Vitro and in Vivo. Molecular Cancer Therapeutics, 5, 1309-1317.
https://doi.org/10.1158/1535-7163.MCT-05-0442 |
| [38] | Lu, Q., Wang, D.S., Chen, C.S., et al. (2005) Struc-ture-Based Optimization of Phenylbutyrate-Derived Histone Deacetylase Inhibitors. Journal of Medicinal Chemistry, 48, 5530-5535. https://doi.org/10.1021/jm0503749 |
| [39] | Zhang, S.W., Gong, C.J., Su, M.B., et al. (2020) Synthesis and in Vitro and in Vivo Biological Evaluation of Tissue-Specific Bisthiazole Histone Deacetylase (HDAC) Inhibitors. Journal of Medicinal Chemistry, 63, 804-815.
https://doi.org/10.1021/acs.jmedchem.9b01792 |
| [40] | Arts, J., King, P., Marin, 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 |
| [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-Hydroxypyrimidine-5-Carboxamide (CHR-3996), a Class I Selective Orally Active Histone Deacetylase Inhibitor. Journal of Medicinal Chemistry, 53, 8663-8678. https://doi.org/10.1158/1078-0432.CCR-09-0547 |
| [42] | Qian, C., Lai, C.J., Bao, R., et al. (2012) Cancer Network Disruption by a Single Molecule Inhibitor Targeting Both Histone Deacetylase Activity and Phosphatidylinosi-tol 3-Kinase Signaling. Clinical Cancer Research, 18, 4104-4113.
https://doi.org/10.1158/1078-0432.CCR-12-0055 |
| [43] | Moradei, O.M., Mallais, T.C., Frechette, S., et al. (2007) Novel Aminophenyl Benzamide-Type Histone Deacetylase Inhibitors with Enhanced Potency and Selectivity. Journal of Medicinal Chemistry, 50, 5543-5546.
https://doi.org/10.1021/jm701079h |
| [44] | Khan, N., Jeffers, M., Kumar, S., et al. (2008) Determination of the Class and Isoform Selectivity of Small-Molecule Histone Deacetylase Inhibitors. Biochemical Journal, 409, 581-589. https://doi.org/10.1042/BJ20070779 |
| [45] | 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 |
| [46] | Lu, X., Ning, Z., Li, Z., Cao, H. and Wang, X. (2016) De-velopment of Chidamide for Peripheral T-Cell Lymphoma, the First Orphan Drug Approved in China. Intractable & Ra-re Diseases Research, 5, 185-191.
https://doi.org/10.5582/irdr.2016.01024 |
| [47] | Bretz, A.C., Parnitzke, U., Kronthaler, K., et al. (2019) Domatinostat Favors the Immunotherapy Response by Modulating the Tumor Immune Microenvironment (TIME). Journal for Immu-noTherapy of Cancer, 7, 294.
https://doi.org/10.1186/s40425-019-0745-3 |
| [48] | 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: Pharma-cokinetics of CXD101 in Patients with Advanced Cancer. Cancer, 125, 99-108. https://doi.org/10.1002/cncr.31791 |
| [49] | Zhang, Q., Dai, Y., Cai, Z. and Mou, L. (2018) HDAC Inhibitors: Novel Immunosuppressants for Allo- and Xeno- Transplantation. ChemistrySelect, 3, 176-187. https://doi.org/10.1002/slct.201702295 |
| [50] | Suraweera, A., O’Byrne, K.J. and Richard, D.J. (2018) Combination Therapy with Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Po-tential of HDACi. Frontiers in Oncology, 8, Article 92. https://doi.org/10.3389/fonc.2018.00092 |
| [51] | Morel, D., Jeffery, D., Aspeslagh, S., Almouzni, G. and Postel-Vinay, S. (2020) Combining Epigenetic Drugs with Other Therapies for Solid Tumours—Past Lessons and Future Promise. Nature Reviews Clinical Oncology, 17, 91-107.
https://doi.org/10.1038/s41571-019-0267-4 |
