HDAC as onco target: Reviewing the synthetic approaches with SAR study of their inhibitors

Sangwan, Rekha; Rajan, Remya; Mandal, Pintu Kumar

doi:10.1016/j.ejmech.2018.08.073

Cited by 70 publications

(33 citation statements)

References 355 publications

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“…The human HDAC4 gene, located on chromosome 2q37.3, has been found to be involved in initiation and development of various cancers, and functions as an oncogene in many cancers [32][33][34][35][36]. A previous study confirmed HDAC4 as a target of miR-29b-3p in MM cells [25].…”

Section: Discussionmentioning

confidence: 94%

Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p

2019

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Background: Long non-coding RNA taurine up-regulated gene 1 (TUG1) was reportedly involved in initiation and development of several cancers. However, its function and molecular mechanisms in multiple myeloma (MM) are still unclear. The present study aimed to determine the expression status, biological function, and potential mechanisms of TUG1 in the progression of MM. Materials and methods: The expression levels of TUG1 were examined in MM samples and cell lines by real-time quantitative PCR. The effects of TUG1 on MM cells proliferation and apoptosis were assessed using Cell Counting Kit-8 assay and flow cytometry respectively. MiRNAs-targeted sites in TUG1 were screened by Starbase2.0 and were identified by RNA immunoprecipitation assay combined with luciferase reporter assay. Results: The expression levels of TUG1 were markedly increased in MM samples and cell lines. Knockdown of TUG1 significantly suppressed the proliferation, induced cell cycle arrest at G1/G0 phase, and promoted apoptosis of MM cells. In exploring the regulatory mechanism, miR-29b-3p was confirmed to be a direct target of TUG1, and repression of miR-29b-3p could partially rescue the effect TUG1 knockdown on MM cell proliferation, cycle, and apoptosis. In addition, TUG1 positively modulated histone deacetylases 4 (HDAC4, a target of miR-29b-3p) expression through sponging of miR-29b-3p in MM cells. Conclusion: These findings suggested that TUG1 exerted an oncogenic role in MM by acting as a competing endogenous RNA of miR-29b-3p, and implied the potential application of TUG1 in treatment for MM.

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Section: Discussionmentioning

confidence: 94%

Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p

2019

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“…2D displayed the binding interaction of SAHA at active site of HDAC8, the hydroxamic acid group of SAHA makes the same contacts to the Zn 2+ and active-site residues. 63 Based on ZBG chemical structures, HDACis could be divided into ve main classes: hydroxamates, cyclic peptides, benzamides, short-chain fatty acids, ketones and others. 64,65 Among which, HDACis containing hydroxamates are the most investigated and potent.…”

Section: Histone Deacetylase Inhibitors (Hdacis)mentioning

confidence: 99%

Next-generation of selective histone deacetylase inhibitors

Yang

Zhao

et al. 2019

RSC Adv.

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“…Cancer is one of the most mortal diseases in the world [1]. In addition to genetic factors, the occurrence of cancer also involves epigenetic modifications including covalent modifications of DNA (methylation and demethylation) and histones [2][3][4][5][6]. Epigenetic regulations achieve reversible modification process through the corresponding enzymes.…”

Section: Introductionmentioning

confidence: 99%

“…Classes I (1,2,3,8), II (4,5,6,7,9,10) and IV (11) HDACs are Zn 2+ -dependent enzymes, while class III HDACs (SIRT1-7) require NAD + for their activities [16][17][18]. Five HDACis, vorinostat (1, SAHA) [19], bellinostat (2,PXD101) [20], panobinostat (3,LBH589) [21], romidepsin (4,FK228) [22] and chidamide (5,CS055) [23] (Figure 1), have been approved on the market for the treatment of cutaneous T-cell lymphoma (CTCL), multiple myeloma (MM) or peripheral T-cell lymphoma (PTCL), and more than 20 other inhibitors are at different stages of clinical trials. However, most HDACis displayed suboptimal results against solid tumors, so it is important to develop novel HDACis to achieve high potency against solid malignancy.…”

Section: Introductionmentioning

confidence: 99%

Development of Coumarin-Based Hydroxamates as Histone Deacetylase Inhibitors with Antitumor Activities

et al. 2020

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Histone deacetylases (HDACs) have been proved to be promising targets for the treatment of cancer, and five histone deacetylase inhibitors (HDACis) have been approved on the market for the treatment of different lymphomas. In our previous work, we designed a series of novel coumarin-containing hydroxamate HDACis, among which compounds 6 and 7 displayed promising activities against tumor growth. Based on a molecular docking study, we further developed 26 additional analogues with the aim to improve activity of designed compounds. Several of these new derivatives not only showed excellent HDAC1 inhibitory effects, but also displayed significant growth inhibitory activities against four human cancer cell lines. Representative compounds, 13a and 13c, showed potent anti-proliferative activities against solid tumor cell lines with IC50 values of 0.36–2.91 µM and low cytotoxicity against Beas-2B and L-02 normal cells. Immunoblot analysis revealed that 13a and 13c dose-dependently increased the acetylation of histone H3 and H4. Importantly, the two compounds displayed much better anti-metastatic effects than SAHA against the MDA-MB-231 cell line. Moreover, 13a and 13c arrested MDA-MB-231 cells at G2/M phase and induced MDA-MB-231 cell apoptosis. Finally, the molecular docking study rationalized the high potency of compound 13c.

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HDAC as onco target: Reviewing the synthetic approaches with SAR study of their inhibitors

Cited by 70 publications

References 355 publications

Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p

Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p

Next-generation of selective histone deacetylase inhibitors

Development of Coumarin-Based Hydroxamates as Histone Deacetylase Inhibitors with Antitumor Activities

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