Histone deacetylases as targets for treatment of multiple diseases

Tang, Jinhua; H, Yan; Zhuang, Songlin

doi:10.1042/cs20120504

Cited by 166 publications

(151 citation statements)

References 132 publications

(146 reference statements)

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“…Hyperacetylation [2,24,25] results in an increase in the space between the nucleosome and the DNA that is wrapped around it. The opening of chromatin structure subsequently provides the access for gene transcription.…”

Section: Hdac6 Inhibitormentioning

confidence: 99%

“…Classification on specificity [2] CLASS I HDAC specific Romidepsin, MS-275 and mocetinostat are well-thought-out to be class I-specific. [21] Class I and class IIa HDACs Inhibitors SAHA, TSA, panobinostat, belinostat and resminostat are pan-deacetylase inhibitors.…”

Section: Omprakash World Journal Of Pharmacy and Pharmaceutical Sciementioning

confidence: 99%

“…[3,4] HDACs are a class of deacetylating enzymes that remove acetyl groups from ϵ-amino groups of lysine residues of histones, as well as non-histone proteins, triggering the condensation of chromatin structure and thus repressing gene expression. [5,6] HDACs are classified into four groups [2] Class I and II are referred to as "classical" HDACs.…”

Section: Hdacsmentioning

confidence: 99%

“…[13] CLASSIFICATION OF HDACs [2] Acetylation and deacetylation are structured by two groups of enzymes: HATs (histone acetyltransferases) and HDACs (histone deacetylases).…”

Section: Hdacsmentioning

confidence: 99%

“…Therefore, it is essential to determine the role of individual HDACs in diabetic nephropathy and develop HDAC inhibitors with better specificity. [11] CLASSIFICATION OF HDAC INHIBITORS (HDACI) [2] Chemical based classification [2] HDACIs are compounds that have the capacity to prevent the deacetylation of lysine residues inside the N-terminal tails of histone proteins.…”

Section: Omprakash World Journal Of Pharmacy and Pharmaceutical Sciementioning

confidence: 99%

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Embryonic Life of Hdac Inhibitors: – In Diabetic Nephropathy

Soni¹

2017

WJPPS

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Section: Hdac6 Inhibitormentioning

confidence: 99%

Section: Omprakash World Journal Of Pharmacy and Pharmaceutical Sciementioning

confidence: 99%

Section: Hdacsmentioning

confidence: 99%

“…[13] CLASSIFICATION OF HDACs [2] Acetylation and deacetylation are structured by two groups of enzymes: HATs (histone acetyltransferases) and HDACs (histone deacetylases).…”

Section: Hdacsmentioning

confidence: 99%

Section: Omprakash World Journal Of Pharmacy and Pharmaceutical Sciementioning

confidence: 99%

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Embryonic Life of Hdac Inhibitors: – In Diabetic Nephropathy

Soni¹

2017

WJPPS

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Pioneering first‐in‐class FAAH‐HDAC inhibitors as potential multitarget neuroprotective agents

Papa,

Cursaro,

Pozzetti

et al. 2023

Archiv der Pharmazie

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Aiming to simultaneously modulate the endocannabinoid system (ECS) functions and the epigenetic machinery, we selected the fatty acid amide hydrolase (FAAH) and histone deacetylase (HDAC) enzymes as desired targets to develop potential neuroprotective multitarget‐directed ligands (MTDLs), expecting to achieve an additive or synergistic therapeutic effect in oxidative stress‐related conditions. We herein report the design, synthesis, and biological evaluation of the first‐in‐class FAAH‐HDAC multitarget inhibitors. A pharmacophore merging strategy was applied, yielding 1‐phenylpyrrole‐based compounds 4a–j. The best‐performing compounds (4c, 4f, and 4h) were tested for their neuroprotective properties in oxidative stress models, employing 1321N1 human astrocytoma cells and SHSY5 human neuronal cells. In our preliminary studies, compound 4h stood out, showing a balanced nanomolar inhibitory activity against the selected targets and outperforming the standard antioxidant N‐acetylcysteine in vitro. Together with 4f, 4h was also able to protect 1321N1 cells from tert‐butyl hydroperoxide or glutamate insult. Our study may provide the basis for the development of novel MTDLs targeting the ECS and epigenetic enzymes.

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Unravelling HDAC Selectivity for Erasing Acetyl Mark on Lys‐5 of Histone H2B

Shukla,

Murmu,

Mora

et al. 2024

ChemBioChem

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The reversible acetylation of specific Lysine residues of histones plays crucial role in the epigenetic regulation of chromatin activity. Importantly, perturbations of acetylation‐deacetylation dynamics have important implications for cancer and neurological disorders. There are 18 human HDACs including sirtuins. The site‐selective acetyl eraser specificity of HDACs is poorly defined. Deciphering the site specificity preference of HDACs from a gamut of lysine in histones may be critical for targeted inhibitor development and delineation of regulatory mechanisms associated with chromatin. Here, we have interrogated the propensity of HDACs to erase acetyl mark at Lys5 of H2B namely, H2BK5Ac engineered by a peptide ligation reaction catalyzed by transpeptidase sortase. HDACs and Sirtuins were individually over‐expressed in HEK293 cells and the deacetylation propensity of respective cell lysates was evaluated against H2BK5Ac for initial screening of potential acetyl erasers. This screen indicated HDAC1 as the prime eraser of acetyl mark in H2BK5Ac. The propensity of HDAC1 to erase acetyl mark of H2BK5Ac was further probed with semisynthetic designer nucleosomes with whole cell lysates, recombinant enzyme, and specific inhibitors. Consistent with the above data, siRNA knockdown of HDAC1 and closely related HDAC3 in HEK293 cells prevented the loss of H2BK5 acetylation.

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Histone deacetylases as targets for treatment of multiple diseases

Cited by 166 publications

References 132 publications

Embryonic Life of Hdac Inhibitors: – In Diabetic Nephropathy

Embryonic Life of Hdac Inhibitors: – In Diabetic Nephropathy

Pioneering first‐in‐class FAAH‐HDAC inhibitors as potential multitarget neuroprotective agents

Unravelling HDAC Selectivity for Erasing Acetyl Mark on Lys‐5 of Histone H2B

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