Last update 01 Nov 2024

HDAC10 x HDAC3 x HDAC2 x HDAC1 x HDAC6 x HDAC8

Last update 01 Nov 2024

Basic Info

Related Targets

HDAC10HDAC3HDAC2[+3]

Drugs associated with HDAC10 x HDAC3 x HDAC2 x HDAC1 x HDAC6 x HDAC8

5e(TES Pharma)

Target

HDAC1 x HDAC10 x HDAC2 x HDAC3 x HDAC6 x HDAC8

Mechanism

HDAC1 modulators [+5]

Active Org.

Fudan University

Originator Org.

TES Pharma SRL

Active Indication

Ovarian Epithelial Carcinoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with HDAC10 x HDAC3 x HDAC2 x HDAC1 x HDAC6 x HDAC8

100 Translational Medicine associated with HDAC10 x HDAC3 x HDAC2 x HDAC1 x HDAC6 x HDAC8

0 Patents (Medical) associated with HDAC10 x HDAC3 x HDAC2 x HDAC1 x HDAC6 x HDAC8

Literatures (Medical) associated with HDAC10 x HDAC3 x HDAC2 x HDAC1 x HDAC6 x HDAC8

15 Jun 2023·Nature communicationsQ1 · CROSS-FIELD

Chemoproteomic target deconvolution reveals Histone Deacetylases as targets of (R)-lipoic acid.

Q1 · CROSS-FIELD

ArticleOA

Author: Deline, Marshall L ; Steimbach, Raphael R ; Fromme, Tobias ; Klingenspor, Martin ; Matthias, Patrick ; Médard, Guillaume ; Wang, Longlong ; Chang, Yun-Chien ; Lechner, Severin ; Kuster, Bernhard ; Miller, Aubry K

Lipoic acid is an essential enzyme cofactor in central metabolic pathways. Due to its claimed antioxidant properties, racemic (R/S)-lipoic acid is used as a food supplement but is also investigated as a pharmaceutical in over 180 clinical trials covering a broad range of diseases. Moreover, (R/S)-lipoic acid is an approved drug for the treatment of diabetic neuropathy. However, its mechanism of action remains elusive. Here, we performed chemoproteomics-aided target deconvolution of lipoic acid and its active close analog lipoamide. We find that histone deacetylases HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are molecular targets of the reduced form of lipoic acid and lipoamide. Importantly, only the naturally occurring (R)-enantiomer inhibits HDACs at physiologically relevant concentrations and leads to hyperacetylation of HDAC substrates. The inhibition of HDACs by (R)-lipoic acid and lipoamide explain why both compounds prevent stress granule formation in cells and may also provide a molecular rationale for many other phenotypic effects elicited by lipoic acid.

01 Mar 2022·Asian Pacific Journal of Cancer Prevention

Differential Expression of Zinc-Dependent HDAC Subtypes and their Involvement in Unique Pathways Associated with Carcinogenesis

Article

Author: Purohit, Purvi ; Ramteke, Abhilash ; Choudhury, Chinmayee ; Ukey, Shweta ; Sharma, Praveen

OBJECTIVEThe present study aims to identify the effect of ZnHDACs expression on the survival of the patients. Further, reveal the unique and common genes associated with each ZnHDACs and their associated pathways.METHODSThe patient data was obtained from the Cancer Genome Atlas Program (TCGA) database and was analyzed using cBioportal and Gene Expression Profiling Interactive Analysis 2(GEPIA2) online tools. Protein-protein interactions and functional interactomic analysis were done using STRING, DAVID, and KEGG pathway databases.RESULTSHDAC1, 2, 8, 11 were over-expressed and, HDAC4, 5, 6, 7, and 10 were down-regulated in all the cancer types, but there are few exceptional expression patterns such as HDAC7 and HDAC10 overexpression in HNSC, HDAC3 down-regulation in LUAD, and PRAD. The unique genes interacting with each ZnHDACs provided a better understanding of ZnHDAC's putative role in carcinogenesis. The present study reported that JARID2, stem cell regulation gene uniquely interacts with HDAC1, BPTF-CHRAC-BAZIA axis, enzymes for chromatin modeling selectively interacting with only HDAC2, HDAC3 in H2A acetylation via DMAP1 and YEATS4. HDAC6 associated unique genes regulate protein stability, HDAC7 in subnuclear localization and splicing, HDAC8 in telomere maintenance, HDAC9 in chromosomal rearrangements, and HDAC11 in maintaining histone core and folding.CONCLUSIONThe unique genes and pathways associated with a particular ZnHDACs could provide a wide window for interrogating these genes for obtaining putative drug targets.

03 Jul 2020·ChemMedChemQ3 · MEDICINE

Design and Synthesis of Dihydroxamic Acids as HDAC6/8/10 Inhibitors

Q3 · MEDICINE

Article

Author: Herbst‐Gervasoni, Corey J. ; Ridinger, Johannes ; Osko, Jeremy D. ; Steimbach, Raphael R. ; Géraldy, Magalie ; Sehr, Peter ; Morgen, Michael ; Miller, Aubry K. ; Gunkel, Nikolas ; Porter, Nicholas J. ; Oehme, Ina ; Witt, Olaf ; Hellweg, Lars ; Christianson, David W.

AbstractWe report the synthesis and evaluation of a class of selective multitarget agents for the inhibition of HDAC6, HDAC8, and HDAC10. The concept for this study grew out of a structural analysis of the two selective inhibitors Tubastatin A (HDAC6/10) and PCI‐34051 (HDAC8), which we recognized share the same N‐benzylindole core. Hybridization of the two inhibitor structures resulted in dihydroxamic acids with benzyl‐indole and ‐indazole core motifs. These substances exhibit potent activity against HDAC6, HDAC8, and HDAC10, while retaining selectivity over HDAC1, HDAC2, and HDAC3. The best substance inhibited the viability of the SK‐N‐BE(2)C neuroblastoma cell line with an IC50 value similar to a combination treatment with Tubastatin A and PCI‐34051. This compound class establishes a proof of concept for such hybrid molecules and could serve as a starting point for the further development of enhanced HDAC6/8/10 inhibitors.

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