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 (189)
Related Products (189)
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HDAC1-IN-8
0 ImagesCat. No.: HY-168477CAS No.: 3066143-73-2HDAC1-IN-8 (compound 5c) is a potent and selective HDAC1 inhibitor with IC50 values of 11.94, 22.95, >500 µM for HDAC1, HDAC6, HDAC8, respectively. HDAC1-IN-8 shows antiproliferative activity. HDAC1-IN-8 induces cell cycle arrest at G1 and G2/M. HDAC1-IN-8 induces autophagy. HDAC1-IN-8 shows anticancer activity and has the potential for the research of lung cancer.
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PROTAC HDAC8 Degrader-1
0 ImagesCat. No.: HY-163920CAS No.: 3057302-08-3
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HDAC8-IN-6
0 ImagesCat. No.: HY-163143CAS No.: 3036403-81-0HDAC8-IN-6 (compound 3) is a potent HDAC8 inhibitor with an IC50 of 5.1 μM. HDAC8-IN-6 shows cytotoxicity.
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HDAC6-IN-79
0 ImagesCat. No.: HY-182747HDAC6-IN-79 is a HDAC6 inhibitor with an IC50 of 98.40 nM, and it also exhibits inhibitory activity against other HDAC subtypes (HDAC1: 639.0 nM, HDAC2: 798.9 nM, HDAC8: 865.7 nM, HDAC4: 1187 nM). HDAC6-IN-79 induces acetylation of α-tubulin and histone H3, reduces the viability of cancer cells, activates the autophagy pathway and induces apoptosis. HDAC6-IN-79 can be used for research related to urothelial carcinoma (bladder cancer).
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TH-6
0 ImagesCat. No.: HY-149029CAS No.: 3031349-25-1
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HDAC-IN-45
0 ImagesCat. No.: HY-150577CAS No.: 2421122-61-2HDAC-IN-45 (Compound 14) is a small molecule HDAC inhibitor and has anticancer activity, also can forms a hydrogen bond with residue Y303. HDAC-IN-45 (Compound 14) has substantial inhibitory effects towards HDAC1, 2 and 3 isoforms with IC50 values of 0.108, 0.585 and 0.563 μM respectively.
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ROCK/HDAC-IN-1
0 ImagesCat. No.: HY-168650ROCK/HDAC-IN-1 (Compound 10h) is an orally active ROCK/HDAC inhibitor. ROCK/HDAC-IN-1 inhibits ROCK1/2 (IC50: 254.9 nM, 58.18 nM) and HDAC1/2/3/6/8 (IC50: 9.09, 8.03, 6.26, 0.41, 7.69 nM). ROCK/HDAC-IN-1 stimulates the activation of DAMPs, specifically Calreticulin (CRT) exposure and HMGB1 release, indicating that it is a potential ICD inducer.. ROCK/HDAC-IN-1 has antiproliferative activity against breast cancer cells (IC50: 0.37 μM for MDA-MB-231 cell), and inhibits tumor growth and activates T cells without apparent toxicity.
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PROTAC HDAC8 Degrader-4
0 ImagesCat. No.: HY-181024PROTAC HDAC8 Degrader-3 (Compound BP6) is an efficient, selective and low-toxicity HDAC8 PROTAC degrader with a DC50 of 80 nM. PROTAC HDAC8 Degrader-3 exhibits IC50 of PROTAC for HDAC8 and CRBN of 0.26 and 30 μM respectively. PROTAC HDAC8 Degrader-3 increases the level of Ac-SMC3, stabilizes p53 and sensitizes targeted reagents (such as Idasanutlin (HY-15676)), demonstrating its great potential in combination therapy.
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HDAC-IN-36
0 ImagesCat. No.: HY-146684CAS No.: 2482992-54-9
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HDAC8-IN-16
0 ImagesCat. No.: HY-182035CAS No.: 2464465-06-1HDAC8-IN-16 is a selective histone deacetylase 8 (HDAC8) inhibitor with an IC50 of 0.16 μM. HDAC8-IN-16 induces cell apoptosis, triggers G2/M phase cell cycle arrest, and moderately inhibits cancer cell proliferation. HDAC8-IN-16 is applicable to relevant research on colorectal cancer.
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HDAC-IN-39
0 ImagesCat. No.: HY-146392CAS No.: 2414046-33-4HDAC-IN-39 (compound 16c) is a potent HDAC inhibitor, with IC50 values of 1.07 μM (HDAC1), 1.47 μM (HDAC2), and 2.27 μM (HDAC3), respectively. HDAC-IN-39 also significantly inhibits microtubule polymerization. HDAC-IN-39 induces cell cycle arrest at the G2/M phase. HDAC-IN-39 displays promising anticancer activity against resistant cancer cells.
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DS-103
0 ImagesCat. No.: HY-173064DS-103 is an inhibitor for HDAC that inhibits HDAC1, HDAC2, HDAC3, HDAC6 and HDAC8 with IC50s of 0.029, 0.123, 0.022, 0.367 and 9.26 μM, respectively. DS-103 inhibits Plasmodium falciparum 3D7 with IC50 of 5.08 μM. DS-103 exhibits cytotoxicity in cells A2780 and Cal27 with IC50 of 1.48 μM and 1.47 μM, reverses Cisplatin (HY-17394) resistance in A2780 and Cal27 with IC50 of 4.62 μM and 2.23 μM. DS-103 exhibits synergistic effect with Cisplatin (HY-17394), enhances Cisplatin-induced apoptosis.
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TNI-97
0 ImagesCat. No.: HY-175030CAS No.: 2790425-52-2TNI-97 is a selective and orally active HDAC6 inhibitor, with an IC50 of 0.2 nM. TNI-97 potently inhibited TNBC cell MDA-MB-453 growth and clonogenicity. TNI-97 induces PANoptosis including apoptosis, necroptosis and pyroptosis in MDA-MB-453 cells. TNI-97 shows antitumor activity in the mice carrying the MDA-MB-453 xenograft or carrying murine-derived TNBC cell allografts. TNI-97 can be used for the study of triple-negative breast cancer.
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HDAC10-IN-2
0 ImagesCat. No.: HY-144782CAS No.: 3033417-22-7HDAC10-IN-2 (compound 10c) is a potent and highly selective HDAC10 inhibitor, with an IC50 of 20 nM. HDAC10-IN-2 modulates autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells.
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PROTAC HDAC8 Degrader-3
0 ImagesCat. No.: HY-181023PROTAC HDAC8 Degrader-3 (Compound BP1) is an efficient and selective HDAC8 PROTAC degrader with a DC50 of 20 nM. PROTAC HDAC8 Degrader-3 exhibits IC50 for HDAC8 and CRBN of 0.46 and 7.5 μM, respectively. PROTAC HDAC8 Degrader-3 exhibits potent anti-proliferative activity against MM.1S and HL-60 cells. PROTAC HDAC8 Degrader-3 can be used for research on multiple myeloma and acute myeloid leukemia.
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HDAC8-IN-2
0 ImagesCat. No.: HY-144098CAS No.: 2824131-20-4HDAC8-IN-2 (compound 5o) is a potent HDAC8 inhibitor, with IC50 values of 0.27 and 0.32 μM for smHDAC8 (Schistosoma mansoni histone deacetylase 8) and hHDAC8, respectively. HDAC8-IN-2 shows significant killing of the schistosome larvae. HDAC8-IN-2 markedly impairs egg laying of adult worm pairs.
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FT108
0 ImagesCat. No.: HY-182720CAS No.: 2379645-28-8FT108 is a selective HDAC6 inhibitor with an IC50 of 0.026 μM. FT108 exhibits only modest in vitro activity against HDAC3 and HDAC8 with IC50 values of 6.68 and 4.07 μM. FT108 increases acetylation of tubulin and has little to no effect on acetylated histone H3 levels. FT108 lacks activity against myeloproliferative neoplasm cell lines, and does not suppress JAK2 phosphorylation or its downstream targets pSTAT3 and pSTAT5.
