Are inhibitors of histone deacetylase 8 (HDAC8) effective in hematological cancers especially acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)?

被引：21

作者：

Amin, Sk Abdul ^{[1
,2
]}

Khatun, Samima ^{[3
]}

Gayen, Shovanlal ^{[3
]}

Das, Sanjib ^{[1
]}

Jha, Tarun ^{[1
]}

机构：

[1] Jadavpur Univ, Dept Pharmaceut Technol, Div Med & Pharmaceut Chem, Nat Sci Lab, Kolkata 700032, India

[2] JIS Univ, Dept Pharmaceut Technol, 81 Nilgunj Rd, Kolkata, West Bengal, India

[3] Jadavpur Univ, Dept Pharmaceut Technol, Lab Drug Design & Discovery, Kolkata 700032, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 258卷

关键词：

Cancer; Hematological malignancy; HDAC; HDAC8; inhibitor; Enzyme selectivity; HYDROXAMIC ACID-DERIVATIVES; BIOLOGICAL EVALUATION; DRUG DISCOVERY; CELL-GROWTH; DNA-BINDING; P53; DESIGN; ACETYLATION; POTENT; THERAPY;

D O I：

10.1016/j.ejmech.2023.115594

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Histone deacetylase 8 (HDAC8) aberrantly deacetylates histone and non-histone proteins. These include structural maintenance of chromosome 3 (SMC3) cohesin protein, retinoic acid induced 1 (RAI1), p53, etc and thus, regulating diverse processes such as leukemic stem cell (LSC) transformation and maintenance. HDAC8, one of the crucial HDACs, affects the gene silencing process in solid and hematological cancer progressions especially on acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). A specific HDAC8 inhibitor PCI-34051 showed promising results against both T-cell lymphoma and AML. Here, we summarize the role of HDAC8 in hematological malignancies, especially in AML and ALL. This article also introduces the structure/function of HDAC8 and a special attention has been paid to address the HDAC8 enzyme selectivity issue in hematological cancer especially against AML and ALL.

引用

页数：26

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