HDAC6
HDAC6 (histone deacetylase 6) is a unique class IIb histone deacetylase that localizes predominantly in the cytoplasm and preferentially targets non-histone substrates rather than chromatin-associated proteins[1][2]. HDAC6 regulates fundamental cellular functions through deacetylation of α-tubulin, Hsp90, and ubiquitin-associated protein complexes, thereby controlling microtubule dynamics, protein trafficking, stress responses, and protein quality-control mechanisms[2][3][4]. Mechanistically, HDAC6 functions at the intersection of the ubiquitin-proteasome system and autophagy-related pathways, where its ubiquitin-binding capability facilitates the processing and clearance of misfolded or aggregated proteins[3][4]. Therefore, HDAC6 has emerged as an important regulator of cellular proteostasis and cytoskeletal remodeling in both physiological and pathological contexts[2][3]. In disease models, HDAC6 has been implicated in cancer progression, neurodegenerative disorders, and inflammatory conditions through its effects on cell motility, intracellular transport, protein aggregation, and stress signaling pathways[2][4][5]. Increased HDAC6 activity promotes α-tubulin deacetylation and influences processes associated with tumor cell migration and metastasis, while modulation of HDAC6 activity alters axonal transport and protein aggregate handling in neurodegenerative disease models[4][5]. Compared with related HDAC isoforms, HDAC6 is distinguished by its predominantly cytoplasmic localization, preference for non-histone substrates, dual catalytic domains, and zinc-finger ubiquitin-binding domain, features that confer specialized biological functions not shared by most nuclear HDAC family members[2][5]. For experimental applications, HDAC6-selective inhibitors have become widely used chemical probes because they enable investigation of HDAC6-dependent signaling and protein homeostasis pathways while potentially reducing the off-target effects associated with pan-HDAC inhibition[3][6].
References:
- [1]. Park SY, et al. A short guide to histone deacetylases including recent progress on class II enzymes. Exp Mol Med. 2020 Feb;52(2):204-212. [Content Brief]
- [2]. Simões-Pires C, et al. HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs? Mol Neurodegener. 2013 Jan 29;8:7. doi: 10.1186/1750-1326-8-7. PMID: 23356410; PMCID: PMC3615964. [Content Brief]
- [3]. Brindisi M, et al. Old but Gold: Tracking the New Guise of Histone Deacetylase 6 (HDAC6) Enzyme as a Biomarker and Therapeutic Target in Rare Diseases. J Med Chem. 2020 Jan 9;63(1):23-39. [Content Brief]
- [4]. HDAC6 gene information from NCBI.
- [5]. Li G, et al. HDAC6 α-tubulin deacetylase: a potential therapeutic target in neurodegenerative diseases. J Neurol Sci. 2011 May 15;304(1-2):1-8. [Content Brief]
- [6]. Zhang Y, et al. Tanshinone IIA sodium sulfonate facilitates endocytic HMGB1 uptake. Biochem Pharmacol. 2012 Dec 1;84(11):1492-500. [Content Brief]
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HDAC6 Related Products (326)
Related Products (326)
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Antibodies (2)
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GSK-3β/HDAC-IN-2
0 ImagesCat. No.: HY-174398GSK-3β/HDAC-IN-2 is a potent inhibitor of GSK-3β (IC50 = 0.04 μM), HDAC2 (IC50 = 1.05 μM, Ki = 0.070 μM) and HDAC6 (IC50 = 1.52 μM, Ki = 0.017 μM). GSK-3β/HDAC-IN-2 inhibits HDAC2 and HDAC6 activities and blocks tau hyperphosphorylation. GSK-3β/HDAC-IN-2 exerts neuroprotective effects and shows no significant toxicity. GSK-3β/HDAC-IN-2 can be used in the research of Alzheimer's disease.
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cGAS/HDAC-IN-1
0 ImagesCat. No.: HY-184398cGAS/HDAC-IN-1 is an orally active dual cGAS/HDAC inhibitor that exhibits potent inhibitory activity against human and mouse cGAS (IC50: 0.17 and 1.80 μM, respectively) and moderate activity against HDAC3 and HDAC6 (IC50: 1.2 and 0.4 μM, respectively). cGAS/HDAC-IN-1 directly suppresses cGAS activity and increases its acetylation levels via HDAC3 inhibition. cGAS/HDAC-IN-1 is effective in murine models of inflammatory bowel disease and Aicardi-Goutières syndrome, and can be used in research on cGAS-dependent disorders.
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F2F-202
0 ImagesCat. No.: HY-184165F2F-202 is a selective HDAC6 inhibitor with an IC50 of 7.1 nM, exhibiting high selectivity toward HDAC1. F2F-202 does not directly bind to or inhibit the Hda1 protease activity of Candida albicans itself, but reduces the mRNA transcription level of the Hda1 gene. When combined with Voriconazole (HY-76200), F2F-202 decreases the yeast-hypha transition rate of azole-resistant Candida albicans and impairs the antioxidant response of azole-resistant Candida albicans. F2F-202 can be used in studies related to azole-resistant Candida albicans infections.
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SHN7
0 ImagesCat. No.: HY-184706CAS No.: 3126116-06-8SHN7 is a selective HDAC1/HDAC6 inhibitor, NQO1 substrate and ROS inducer, with an IC50 of 30 nM against HDAC1 and an IC50 of 10 nM against HDAC6. SHN7 inhibits STAT3 with a Kd of 8.9 μM. SHN7 arrests the cell cycle at the G2/M phase and induces Apoptosis. SHN7 exhibits anti-tumor effects in triple-negative breast cancer (TNBC) xenograft models. SHN7 can be used for the research of triple-negative breast cancer.
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HDAC6-IN-44
0 ImagesCat. No.: HY-162630HDAC6-IN-44 (compound H10) is a selective HDAC6 inhibitor with an IC50 value of 8.97 nM. HDAC6-IN-44 can inhibit the idiopathic pulmonary fibrosis (IPF) phenotype and exhibits antifibrotic activity. Additionally, HDAC6-IN-44 reduces fibrogenesis in a bleomycin-induced pulmonary fibrosis mouse model and demonstrates good metabolic stability. HDAC6-IN-44 holds promise for research in the field of idiopathic pulmonary fibrosis.
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HDAC6-IN-34
0 ImagesCat. No.: HY-163368CAS No.: 1432508-73-0HDAC6-IN-34 (compound 21) is an oral active and selective HDAC6 inhibitor with the IC50 of 18 nM. HDAC6-IN-34 increases the acetylation level of tubulin without affecting histone acetylation in cutaneous T-cell lymphoma cells and inhibits TNF-α secretion in LPS (HY-D1056)-stimulated macrophage cells. HDAC6-IN-34 shows excellent anti-arthritic efficacy in rat.
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mTOR/HDAC6-IN-1
0 ImagesCat. No.: HY-144449CAS No.: 2986747-52-6
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HDAC6-IN-86
0 ImagesCat. No.: HY-187210CAS No.: 2271229-98-0HDAC6-IN-86 is a histone deacetylase 6 (HDAC6) inhibitor with an IC50 of 74 nM, and it exhibits high selectivity for HDAC1. HDAC6-IN-86 induces cell apoptosis, triggers G2/M phase cell cycle arrest, and inhibits the proliferation of glioma cells. HDAC6-IN-86 can be used for the research of glioblastoma multiforme (GBM).
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HDAC-IN-76
0 ImagesCat. No.: HY-161984HDAC-IN-76 (compound 6i) is a histone deacetylase (HDAC) inhibitor. HDAC-IN-76 IC50 values of 30 nM and 98 nM for Pf3D7 (chloroquine (HY-17589A) drug-susceptible strain) and PfDd2 (chloroquine (HY-17589A) drug-resistant strain), has a highly potent antimalarial activity against asexual blood-stage Plasmodium, respectively, and exhibits selective inhibition against parasites, with IC50 values of 7 nM and 9 nM for human HDAC1 and HDAC6, respectively, while inhibiting PfHDAC1.
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NN-429
0 ImagesCat. No.: HY-182649CAS No.: 2490284-32-5
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JAK/HDAC-IN-2
0 ImagesCat. No.: HY-149283CAS No.: 3029138-43-7JAK/HDAC-IN-2 is a potent 2-amino-4-phenylaminopyrimidine JAK/HDAC dual-target inhibitor. JAK/HDAC-IN-2 potently inhibits HDAC3/6 and JAK1/2 at nanomolar levels. JAK/HDAC-IN-2 has proapoptotic activity and inhibits histone deacetylation and STAT3 phosphorylation. JAK/HDAC-IN-2 presents remarkable antiproliferative activity in both hematological malignancies and solid cancers.
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PROTAC HDAC6 degrader 4
0 ImagesCat. No.: HY-172359PROTAC HDAC6 degrader 4 (Compound 17c) is the PROTAC degrader for HDAC6 with a DC50 of 14 nM. PROTAC HDAC6 degrader 4 exhibits inhibitory activit against HDAC1, HDAC2, HDAC3 and HDAC6 with IC50s of 2.2, 2.37, 0.61 and 0.295 μM, respectively. (Pink: ligand for target protein HDAC6 ligand-3 (HY-172360); Black: linker (HY-138387); Blue: ligand for cereblon E3 ligase (HY-W093272))
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PROTAC HDAC6/ERα degrader 1
0 ImagesCat. No.: HY-187387CAS No.: 3092711-76-4PROTAC HDAC6/ERα degrader 1 is a dual-target PROTAC that targets HDAC6/ERα, with DC50 values of 1.21 μM (HDAC6), 0.28 μM (ERα) in MCF-7 cells and 0.67 μM (HDAC6), 0.14 μM (ERα) in LCC2 cells, respectively. PROTAC HDAC6/ERα degrader 1 selectively degrades ERα and HDAC6 via the proteasomal pathway, inhibits the transcriptional activation of ERα and blocks the estrogen signaling pathway. PROTAC HDAC6/ERα degrader 1 inhibits the function of HDAC6, attenuates hormone responses, and disrupts autophagy-lysosome function. PROTAC HDAC6/ERα degrader 1 induces cell cycle arrest, apoptosis and ferroptosis, and exhibits antiproliferative activity in breast cancer cells. PROTAC HDAC6/ERα degrader 1 can be used for breast cancer research.
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PIM-1/HDAC-IN-1
0 ImagesCat. No.: HY-143233CAS No.: 2897622-19-2PIM-1/HDAC-IN-1 (compound 4d) is a PIM-1 inhibitor, with an IC50 of 343.87 nM. PIM-1/HDAC-IN-1 has strong inhibitory activity and selectivity against HDAC 1 and HDAC 6, with IC50 values of 63.65 and 62.39 nM, respectively. PIM-1/HDAC-IN-1 exhibits apoptosis inducing potential in MCF-7 cell lines. PIM-1/HDAC-IN-1 shows pre-G1 apoptosis and cell cycle arrest at G2/M phase.
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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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HDAC6-IN-71
0 ImagesCat. No.: HY-180829CAS No.: 3062867-16-4HDAC6-IN-71 (Compound 24) is a HDAC6 inhibitor with IC50 values for HDAC6 and HDAC1 of 13.68 and 443.12 nM respectively. HDAC6-IN-71 effectively inhibits the production of NO by mouse macrophages, with its IC50 being 2.31 μM. HDAC6-IN-71 inhibits the HDAC6-NF-κB signaling pathway, reduces the levels of phosphorylated IκB-α and IKK-α/β, and suppresses the expression of downstream inflammatory proteins COX-2 and iNOS. HDAC6-IN-71 significantly alleviates ulcerative colitis in mice.
