组蛋白去乙酰化酶抑制剂的研究进展
Research Progress on Histone Deacetylase Inhibitors
DOI: 10.12677/HJMCe.2023.112015, PDF,  被引量   
作者: 汤玉姜, 周庆发*:中国药科大学理学院,江苏 南京
关键词: 组蛋白去乙酰化酶临床进展癌症Histone Deacetylase Clinical Research Cancer
摘要: 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。
Abstract: 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.
文章引用:汤玉姜, 周庆发. 组蛋白去乙酰化酶抑制剂的研究进展[J]. 药物化学, 2023, 11(2): 116-126. https://doi.org/10.12677/HJMCe.2023.112015

参考文献

[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[5] Jiang, Y., Liu, J. and Chen, D. (2017) Sirtuin Inhibition: Strate-gies, Inhibitors and Therapeutic Potential. Trends in Pharmacological Sciences, 38, 459-472. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[10] Wang, Y. and Wang, H. (2022) The Emerging Role of Histone Deacetylase 1 in Allergic Diseases. Frontiers in Immunology, 13, Article 1027403. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef] [PubMed]
[13] Weïwer, 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. [Google Scholar] [CrossRef] [PubMed]
[14] Kim, J.Y., Cho, H., Yoo, J., et al. (2022) Pathological Role of HDAC8: Cancer and Beyond. Cells, 11, Article 3161. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[21] Seidel, C., Schnekenburger, M., Dicato, M. and Diederich, M. (2015) Histone Deacetylase 6 in Health and Disease. Epigenomics, 7, 103-118. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[23] Cheng, F., Zheng, B., Wang, J., et al. (2021) Histone Deacetylase 10, a Potential Epigenetic Target for therapy. Bioscience Reports, 41. [Google Scholar] [CrossRef
[24] Liu, S.S., Wu, F. and Jin, Y.M. (2020) HDAC11: A Rising Star in Epigenetics. Biomedicine & Pharmacotherapy, 131, Article ID: 110607. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[49] Zhang, Q., Dai, Y., Cai, Z. and Mou, L. (2018) HDAC Inhibitors: Novel Immunosuppressants for Allo- and Xeno- Transplantation. ChemistrySelect, 3, 176-187. [Google Scholar] [CrossRef
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]