HDAC8
HDAC8 (histone deacetylase 8) is a zinc-dependent class I histone deacetylase that regulates chromatin organization and transcription through deacetylation of both histone and nonhistone substrates, placing it at the center of epigenetic control mechanisms.[1] Mechanistically, HDAC8 participates in transcriptional regulation, cell-cycle progression, and genome maintenance, and recent evidence shows that HDAC8 activity contributes to replication-fork stability through regulation of the cohesin component SMC3 and suppression of replication-associated stress.[2] These functions connect HDAC8 to biological processes that govern proliferation, differentiation, and cellular homeostasis.[1][2] In disease settings, dysregulated HDAC8 has been implicated in multiple cancers, where it is associated with tumor cell proliferation, metastasis, immune evasion, and drug resistance, supporting its relevance as an epigenetic therapeutic target.[3][1] HDAC8 has also been linked to developmental and genetic disorders, including Cornelia de Lange syndrome and X-linked intellectual disability, indicating functions that extend beyond oncology.[1] Compared with related class I isoforms such as HDAC1, HDAC2, and HDAC3, HDAC8 displays distinct structural and substrate-recognition properties, recognizes both histone and nonhistone proteins, and therefore offers opportunities for isoform-selective pharmacological modulation.[1][4] For experimental applications, selective HDAC8 inhibitors have been developed to minimize the off-target effects associated with pan-HDAC inhibition, and these compounds are widely used to investigate HDAC8-dependent pathways and evaluate therapeutic strategies in cancer and other disease models.[1][4]
References:
- [1]. Chakrabarti A, et al. HDAC8: a multifaceted target for therapeutic interventions. Trends Pharmacol Sci. 2015 Jul;36(7):481-92. doi: 10.1016/j.tips.2015.04.013. Epub 2015 May 23. PMID: 26013035. [Content Brief]
- [2]. Chang TY, et al. Combined HDAC8 and checkpoint kinase inhibition induces tumor-selective synthetic lethality in preclinical models. J Clin Invest. 2024 Oct 22;134(23):e165448. doi: 10.1172/JCI165448. PMID: 39436709; PMCID: PMC11601943. [Content Brief]
- [3]. Kim JY, et al. Pathological Role of HDAC8: Cancer and Beyond. Cells. 2022 Oct 9;11(19):3161. [Content Brief]
- [4]. Fontana A, et al. A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors. Int J Mol Sci. 2022 Sep 2;23(17):10014. doi: 10.3390/ijms231710014. PMID: 36077415; PMCID: PMC9456347. [Content Brief]
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HDAC8 Related Products (188)
Related Products (188)
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Givinostat hydrochloride monohydrate
0 ImagesSynonyms: ITF-2357 hydrochloride monohydrate
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Quisinostat dihydrochloride
0 ImagesSynonyms: JNJ-26481585 dihydrochlorideQuisinostat dihydrochloride (JNJ-26481585 dihydrochloride) is an orally active, potent pan-HDAC inhibitor with IC50s of 0.11 nM, 0.33 nM, 0.64 nM, 0.46 nM, and 0.37 nM for HDAC1, HDAC2, HDAC4, HDAC10 and HDAC11, respectively. Quisinostat dihydrochloride has a broad spectrum antitumoral activity. Quisinostat dihydrochloride can induce autophagy in neuroblastoma cells.
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Thalidomide-4-OH
0 ImagesSynonyms: Cereblon ligand 2; E3 ligase Ligand 2Thalidomide-4-OH (Cereblon ligand 2) is the Thalidomide-based Cereblon ligand used in the recruitment of CRBN protein. Thalidomide-4-OH (Cereblon ligand 2) can be connected to the ligand for protein by a linker to form PROTACs.
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HDAC10-IN-1
0 ImagesCat. No.: HY-144779CAS No.: 3033417-31-8HDAC10-IN-1 (compound 13b) is a potent and highly selective HDAC10 inhibitor, with an IC50 of 58 nM. HDAC10-IN-1 modulates autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells.
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Droxinostat
0 ImagesSynonyms: NS 41080
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CHDI-390576
0 ImagesSynonyms: CHDI00390576CHDI-390576, a potent, cell permeable and CNS penetrant class IIa histone deacetylase (HDAC) inhibitor with IC50s of 54 nM, 60 nM, 31 nM, 50 nM for class IIa HDAC4, HDAC5, HDAC7, HDAC9, respectively, shows >500-fold selectivity over class I HDACs (1, 2, 3) and ~150-fold selectivity over HDAC8 and the class IIb HDAC6 isoform.
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YX968
0 ImagesYX968 is a selective HDAC3/HDAC8 PROTAC dual degrader, with a DC50 value of 1.7 nM against HDAC3 and 6.1 nM against HDAC8. YX968 inhibits cancer cell growth, induces apoptosis, prevents global histone hyperacetylation, and exerts effects via antiproliferative activity. YX968 can be used in research related to triple-negative breast cancer, non-small cell lung cancer, and multiple myeloma.
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HDAC3-IN-T247
0 ImagesHDAC3-IN-T247 is a potent and selective HDAC3 (histone deacetylase 3) inhibitor, with an IC50 of 0.24 µM. HDAC3-IN-T247 induces a selective increase of NF-κB acetylation in HCT116 cells. HDAC3-IN-T247 shows anticancer and antiviral activity. HDAC3-IN-T247 inhibits growth of cancer cells, and activates HIV gene expression in latent HIV-infected cells.
