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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HDAC-IN-50
0 ImagesCat. No.: HY-152146CAS No.: 2653339-26-3HDAC-IN-50 is a potent and orally active FGFR and HDAC dual inhibitor with IC50 values of 0.18, 1.2, 0.46, 1.4, 1.3, 1.6, 2.6, 13 nM for FGFR1, FGFR2, FGFR3, FGFR4, HDAC1, HDAC2, HDAC6, HDAC8, respectively. HDAC-IN-50 induces Apoptosis and cell cycle arrest at G0/G1 phase. HDAC-IN-50 decreases the expression of pFGFR1, pERK, pSTAT3. HDAC-IN-50 shows anti-tumor activity.
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NHNB
0 ImagesCat. No.: HY-115442CAS No.: 106359-61-9NHNB is a selective HDAC8 inhibitor (IC50 = 66.0 μM) and Peptidoglycan N-acetylglucosamine (GlcNAc) deacetylases (PGNGdacs) inhibitor. NHNB shows antibacterial and bactericidal activity against B. anthracis and B. cereus. NHNB can be used for the research of acute myeloid leukemia, Bacillus anthracis infection, and Bacillus cereus infection.
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Tubulin/HDAC-IN-1
0 ImagesCat. No.: HY-150772CAS No.: 2413587-26-3Tubulin/HDAC-IN-1 is a dual tubulin and HDAC-IN-1 inhibitor through CH/π interaction with tubulin and hydrogen bond interaction with HDAC8. Tubulin/HDAC-IN-1 inhibits tubulin polymerization and selectively inhibits HDAC8 (IC50: 150 nM). Tubulin/HDAC-IN-1 has cytotoxicity against various human cancer cells, also arrests cell cycle in the G2/M phase and induces cell apoptosis. Tubulin/HDAC-IN-1 can be used in the research of hematologic and solid tumors such as neuroblastoma, leukemia.
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ZG-126
0 ImagesCat. No.: HY-161778CAS No.: 3049802-32-3ZG-126 is an agonist for vitamin D receptor (VDR) and an inhibitor for histone deacetylase (HDAC) (IC50=0.63-67.6 μM). ZG-126 exhibits cytotoxicity in cancer cells MDA-MB-231 and 4T1. ZG-126 exhibits antitumor and anti-metastatic efficacy against melanoma and triple-negative breast cancer (TNBC) in mouse models. ZG-126 also exhibits anti-inflammatory activity, through the reduction of macrophage infiltration and immunosuppressive M2-polarization.
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PROTAC HDAC8 Degrader-5
0 ImagesCat. No.: HY-189151CAS No.: 3057302-21-0PROTAC HDAC8 Degrader-5 is a selective HDAC8 PROTAC degrader that mediates ubiquitination and proteasomal degradation through the formation of a ternary complex. PROTAC HDAC8 Degrader-5 degrades HDAC8 with a DC50 of 1.8 nM in MDA-MB-231 cells and a DC50 of 4.7 nM in Jurkat cells. PROTAC HDAC8 Degrader-5 inhibits cancer cell migration and proliferation, induces apoptosis through caspase 3/7 activation, and increases acetylated SMC3 and α-tubulin. PROTAC HDAC8 Degrader-5 is useful for cancer-related research, such as leukemia, triple-negative breast cancer, etc..
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Tubulin/HDAC-IN-3
0 ImagesCat. No.: HY-149578Tubulin/HDAC-IN-3 (compound 12a) is a potent tubulin/HDAC dual inhibitor. Tubulin/HDAC-IN-3 effectively disrupts tubulin polymerization (IC50: 5.4 μM). Tubulin/HDAC-IN-3 exhibits potent HDAC1/8 inhibitory activities, with IC50 values of 0.155 and 0.177 μM, respectively. Tubulin/HDAC-IN-3 works through blocking cellular cycle, inducing apoptosis and inhibiting colony formation.
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JN210
0 ImagesCat. No.: HY-189074JN210 is a dual inhibitor of DCN1 and HDAC, with an IC50 of 94.26 nM against human DCN1. JN210 disrupts the UBE2M-DCN1 protein-protein interaction, blocks the neddylation modification of cullin-RING ligases, inhibits HDAC activity and induces histone hyperacetylation. JN210 impairs DNA damage repair function, induces cell apoptosis, exerts cytotoxicity and inhibits tumor growth. JN210 can be used for the research of non-small cell lung cancer.
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HDAC6-IN-43
0 ImagesCat. No.: HY-161524CAS No.: 3037978-19-8HDAC6-IN-43 (compound 26) is a potent HDAC inhibitor. HDAC6-IN-43 effectively inhibits several HDACs, notably HDAC1, HDAC2, and HDAC6 (IC50 < 150 nM), displaying a particularly high sensitivity towards HDAC6 (IC50 = 11 nM). HDAC6-IN-43 can be used for the research of autosomal dominant polycystic kidney disease (ADPKD).
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HDAC-IN-93
0 ImagesCat. No.: HY-178104HDAC-IN-93 is a HDAC inhibitor with promising total pan-HDAC inhibitory activity. HDAC-IN-93 demonstrates significant broad-spectrum antiproliferative activity across various cancer cell lines. HDAC-IN-93 induces cell apoptosis along with necrosis. HDAC-IN-93 can be used for the studies of prostate cancer and breast cancer.
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Quisinostat hydrochloride
0 ImagesCat. No.: HY-15433BCAS No.: 1083078-98-1Synonyms: JNJ26481585 hydrochlorideQuisinostat (JNJ-26481585) hydrochloride is a potent and orally active pan-HDAC inhibitor (HDACi), with IC50 values ranging from 0.11 nM to 0.64 nM for HDAC1, HDAC2, HDAC4, HDAC10 and HDAC11. Quisinostat hydrochloride has a broad spectrum antitumoral activity. Quisinostat hydrochloride can induce autophagy in neuroblastoma cells.
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HDAC-IN-47
0 ImagesCat. No.: HY-151443CAS No.: 3033608-94-2HDAC-IN-47 is an orally active inhibitor of histone deacetylase (HDAC), with IC50s of 19.75 nM (HDAC1), 5.63 nM (HDAC2), 40.27 nM (HDAC3), 57.8 nM (HDAC2), 302.73 nM (HDAC8), respectively. HDAC-IN-47 inhibits autophagy and induces apoptosis via the Bax/Bcl-2 and caspase-3 pathways. HDAC-IN-47 arrests cell cycle at G2/M phase, and shows anti-tumor efficacy in vivo.
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HDAC8-IN-15
0 ImagesCat. No.: HY-181979HDAC8-IN-15 is a selective HDAC8 inhibitor with an IC50 of 0.40 μM. HDAC8-IN-15 increases the acetylation level of the HDAC8 substrate SMC3 without altering the total protein level of SMC3. HDAC8-IN-15 reduces cancer cell viability, inhibits colony formation, slows cell migration, induces apoptosis, and causes cell cycle arrest at the SubG1 phase. HDAC8-IN-15 can be used in studies related to neuroblastoma.
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CM-444
0 ImagesCat. No.: HY-163803CAS No.: 2256079-52-2CM-444 is inhibitor for HDAC (IC50 is 6 nM-0.6 μM) and DNA methyltransferases (DNMT, IC50 is 1.8-2.3 μM). CM-444 is an inducer for the differentiation of acute myeloid leukemia cells. CM-444 exhibits anti-leukemic activity and improves the survival rate in mouse models.
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HDAC8-IN-14
0 ImagesCat. No.: HY-178380HDAC8-IN-14, a curcuminoid derivative, is a selective HDAC8 inhibitor with a Ki of 9 nM. HDAC8-IN-14 induces the production of reactive oxygen species (ROS), disrupts mitochondrial membrane potential, and promotes apoptosis. HDAC8-IN-14 can significantly promote the accumulation of cells in the sub-G0/G1 phase, consistent with apoptotic or necrotic cell death. HDAC8-IN-14 induces upregulation of cytochrome c, cleaved caspase-3, and the pro-apoptotic protein Bak while leaving the anti-apoptotic Bcl-2 levels unaltered. HDAC8-IN-14 can be used for the study of leukemia.
