2. Signaling Pathways
  3. Cell Cycle/DNA Damage
    Epigenetics
  4. HDAC

HDAC

Histone deacetylases

HDAC

Related Products

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HDAC (Histone deacetylases) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on ahistone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone acetyltransferase. HDAC proteins are now also called lysine deacetylases (KDAC), to describe their function rather than their target, which also includes non-histone proteins. Together with the acetylpolyamine amidohydrolases and the acetoin utilization proteins, the histone deacetylases form an ancient protein superfamily known as the histone deacetylase superfamily.

HDAC Isoform Specific Products:

HDAC Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-109015S
    Tucidinostat-d4
    		Inhibitor
    Tucidinostat-d4 is the deuterium labeled Tucidinostat. Tucidinostat is a potent and orally bioavailable HDAC enzymes class I (HDAC1/2/3) and class IIb (HDAC10) inhibitor, with IC50s of 95, 160, 67 and 78 nM, respectively.
    Tucidinostat-d<sub>4</sub>
  • HY-155329
    GK718
    		Inhibitor
    GK718 is a HDAC1/3 inhibitor (IC50: 259 and 139 nM respectively). GK718 increased acetylated histone H3 level in cells. GK718 inhibits Bleomycin (HY-108345) induced pulmonary fibrosis in mice.
    GK718
  • HY-161155
    HDAC6-IN-31
    		Inhibitor
    HDAC6-IN-31 (compound 8m) is a selective HDAC6 inhibitor, with the IC50 value of 0.026 μM, that significantly inhibits the production and release of pro-inflammatory cytokines. While HDAC6 is critically involved in the activation of inflammasomes, HDAC6-IN-31 has the potential to inhibit NLRP3 inflammasome-driven inflammatory diseases. HDAC6-IN-31 also inhibits glioblastoma cell migration.
    HDAC6-IN-31
  • HY-161350
    ALK/HDAC-IN-1
    		Inhibitor
    ALK/HDAC-IN-1 is a dual inhibitor for ALK and HDAC6, with IC50s of 16 nM and 1.03 μM, respectively. ALK/HDAC-IN-1 exhibits antitumor activity.
    ALK/HDAC-IN-1
  • HY-147892
    HDAC-IN-42
    		Inhibitor
    HDAC-IN-42 (compound 14f) is a potent and selective HDAC inhibitor with IC50 values of 0.19 and 4.98 µM for HDAC1 and HDAC6, respectively. HDAC-IN-42 shows anticancer and anti-proliferative activity. HDAC-IN-42 induces apoptosis and cell cycle arrest at G2/M phase.
    HDAC-IN-42
  • HY-115941
    HDAC-IN-9
    		Inhibitor
    HDAC-IN-9 is a potent and selective tubulin and HDAC dual inhibitor. HDAC-IN-9 inhibits the invasion and migration of A549 cells. HDAC-IN-9 shows potent antitumor and antiangiogenic effect in vitro and in vivo.
    HDAC-IN-9
  • HY-145852
    Top/HDAC-IN-2
    		Inhibitor
    Top/HDAC-IN-2 (45b), a Top and HDAC dual inhibitor, exhibits potent antitumor activities and induces apoptosis.
    Top/HDAC-IN-2
  • HY-149474
    HDAC-IN-63
    		Inhibitor
    HDAC-IN-63 (Compound 63) is a dual FLT3/HDAC inhibitor (IC50: 0.844 and 30.0 nM for FLT3 and HDAC1 respectively). HDAC-IN-63 inhibits MV4-11 cell proliferation (IC50: 92 nM. HDAC-IN-63 induces apoptosis and arrests cell cycle in MV4-11 cells. HDAC-IN-63 can be used for research of acute myeloid leukemia (AML).
    HDAC-IN-63
  • HY-152133
    PROTAC HDAC6 degrader 1
    		Degrader
    PROTAC HDAC6 degrader (Compound A6) is a potent and selective PROTAC HDAC6 degrader with a DC50 of 3.5 nM. PROTAC HDAC6 degrader shows promising antiproliferative activity via inducing apoptosis in myeloid leukemia cell lines.
    PROTAC HDAC6 degrader 1
  • HY-151366
    HDAC8/BRPF1-IN-1
    		Inhibitor
    HDAC8/BRPF1-IN-1 (Compound 23a) is a dual inhibitor of HDAC8 and BRPF1 with an IC50 of 443 nM against human HDAC8 and a Kd of 67 nM against human BRPF1. HDAC8/BRPF1-IN-1 shows low in vitro activity against HDAC1 and 6.
    HDAC8/BRPF1-IN-1
  • HY-149721
    HDAC4-IN-1
    		Inhibitor
    HDAC4-IN-1 (compound 1a) is a class IIa HDACI inhibitor (IC50=0.077 μM). HDAC4-IN-1 can enhance Caspase-induced Apoptosis. HDAC4-IN-1 has anticancer activity. HDAC4-IN-1 can be used in the research of drug combination against cancer.
    HDAC4-IN-1
  • HY-169940
    Fibrostat
    		Inhibitor
    Fibrostat (Compound 5n) is a selective HDAC6 inhibitor that exerts antifibrotic effects by inhibiting HDAC6 activity, with an IC50 value of 63 nM. It also exhibits good selectivity over HDAC1, HDAC3, HDAC5, HDAC8, HDAC10, and HDAC11. Fibrostat significantly downregulates fibrotic markers (fibronectin and collagen 1) in fibroblasts. Additionally, Fibrostat demonstrated no toxicity in rat-perfused heart and zebrafish larvae models. Fibrostat shows potential for research into fibrosis-related diseases.
    Fibrostat
  • HY-157215
    HDAC-IN-66
    		Inhibitor
    HDAC-IN-66 (compound 2F) is a selective HDAC inhibitor and Pomalidomide (HY-10984) derivative that potently inhibits hematological tumor cells.
    HDAC-IN-66
  • HY-161783
    HDAC6-IN-45
    		Inhibitor
    HDAC6-IN-45 (Compound 15) is a selective inhibitor for HDAC6 with IC50 of 15.2 nM. HDAC6-IN-45 exhibits neurotrophic through the upregulation of GAP43 and Beta-3 tubulin markers. HDAC6-IN-45 activates the Nrf2 signaling pathway, reduces H2O2-induced ROS production, inhibits apoptosis in PC12, and exhibits neuroprotective efficacy in SCOP-induced zebrafish Alzheimer's Disease models. HDAC6-IN-45 exhibits antioxidant activity and good blood-brain barrier (BBB) permeability.
    HDAC6-IN-45
  • HY-159112
    AW01178
    		Inhibitor
    AW01178 is a Class I HDAC inhibitor. AW01178 induces the upregulation of E-cadherin at both mRNA and protein levels and inhibits the EMT of breast cancer cells.
    AW01178
  • HY-149239
    Topo II/HDAC-IN-2
    		Inhibitor
    Topo II/HDAC-IN-2 (8d) exhibits excellent dual inhibitory activities against Topo II and HDAC. Topo II/HDAC-IN-2 (8d) induces apoptosis.
    Topo II/HDAC-IN-2
  • HY-163207
    sEH/HDAC6-IN-1
    		Inhibitor
    sEH/HDAC6-IN-1 (compound M9) is a selective, orally active dual inhibitor for sEH and HDAC6, with IC50s of 2 nM, 0.72 nM and 5 nM, for human sEH, murine sEH and HDAC6, respectively. sEH/HDAC6-IN-1 reveals analgesic and anti-inflammatory effects.
    sEH/HDAC6-IN-1
  • HY-163503
    HDAC6-IN-38
    		Inhibitor
    HDAC6-IN-38 (Compound Z-7) is an inhibitor for histone deacetylase 6 (HDAC6), with an IC50 of 3.25 nM. HDAC6-IN-38 inhibits proliferation of cells MGC 803.
    HDAC6-IN-38
  • HY-10585AG
    Valproic acid sodium (GMP)
    		Inhibitor
    Valproic acid (Sodium Valproate) sodium is an orally active HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2. Valproic acid sodium activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid sodium is used in the treatment of epilepsy, bipolar disorder, metabolic disease, HIV infection and prevention of migraine headaches.
    Valproic acid sodium (GMP)
  • HY-157889
    ZINC000028464438
    		Inhibitor
    ZINC000028464438 is a selective HDAC11 inhibitor with an IC50 of 3.5 µM. ZINC000028464438 shows almost no inhibition for other HDAC subtypes.
    ZINC000028464438
Cat. No. Product Name / Synonyms Application Reactivity
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Download HDAC Signaling Pathway Map.

TCR, GPCR and HDAC II interaction: Diverse agonists act through G-protein-coupled receptors (GPCRs) to activate the PKC-PKD axis, CaMK, Rho, or MHC binding to antigens stimulates TCR to activate PKD, leading to phosphorylation of class II HDACs. Phospho-HDACs dissociate from MEF2, bind 14-3-3, and are exported to the cytoplasm through a CRM1-dependent mechanism. CRM1 is inhibited by leptomycin B (LMB). Release of MEF2 from class II HDACs allows p300 to dock on MEF2 and stimulate gene expression. Dephosphorylation of class II HDACs in the cytoplasm enables reentry into the nucleus[1].

 

TLR: TLR signaling is initiated by ligand binding to receptors. The recruitment of TLR domain-containing adaptor protein MyD88 is repressed by HDAC6, whereas NF-κB and MTA-1 can be negatively regulated by HDAC1/2/3 and HDAC2, respectively. Acetylation by HATs enhance MKP-1 which inhibits p38-mediated inflammatory responses, while HDAC1/2/3 inhibits MKP-1 activity. HDAC1 and HDAC8 repress, whereas HDAC6 promotes, IRF function in response to viral challenge. HDAC11 inhibits IL-10 expression and HDAC1 and HDAC2 represses IFNγ-dependent activation of the CIITA transcription factor, thus affecting antigen presentation[2][3].

 

IRNAR: IFN-α/β induce activation of the type I IFN receptor and then bring the receptor-associated JAKs into proximity. JAK adds phosphates to the receptor. STATs bind to the phosphates and then phosphorylated by JAKs to form a dimer, leading to nuclear translocation and gene expression. HDACs positively regulate STATs and PZLF to promote antiviral responses and IFN-induced gene expression[2][3].

 

Cell cycle: In G1 phase, HDAC, Retinoblastoma protein (RB), E2F and polypeptide (DP) form a repressor complex. HDAC acts on surrounding chromatin, causing it to adopt a closed chromatin conformation, and transcription is repressed. Prior to the G1-S transition, phosphorylation of RB by CDKs dissociates the repressor complex. Transcription factors (TFs) gain access to their binding sites and, together with the now unmasked E2F activation domain. E2F is then free to activate transcription by contacting basal factors or by contacting histone acetyltransferases, such as CBP, that can alter chromatin structure[4].

 

The function of non-histone proteins is also regulated by HATs/HDACs. p53: HDAC1 impairs the function of p53. p53 is acetylated under conditions of stress or HDAC inhibition by its cofactor CREB binding protein (CBP) and the transcription of genes involved in differentiation is activated. HSP90: HSP90 is a chaperone that complexes with other chaperones, such as p23, to maintain correct conformational folding of its client proteins. HDAC6 deacetylates HSP90. Inhibition of HDAC6 would result in hyperacetylated HSP90, which would be unable to interact with its co-chaperones and properly lead to misfolded client proteins being targeted for degradation via the ubiquitin-proteasome system[5][6].
 

Reference:

[1]. Vega RB, et al. Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5.Mol Cell Biol. 2004 Oct;24(19):8374-85.
[2]. Shakespear MR, et al. Histone deacetylases as regulators of inflammation and immunity. Trends Immunol. 2011 Jul;32(7):335-43.
[3]. Suliman BA, et al. HDACi: molecular mechanisms and therapeutic implications in the innate immune system.Immunol Cell Biol. 2012 Jan;90(1):23-32. 
[4]. Brehm A, et al. Retinoblastoma protein meets chromatin.Trends Biochem Sci. 1999 Apr;24(4):142-5.
[5]. Butler R, et al. Histone deacetylase inhibitors as therapeutics for polyglutamine disorders.Nat Rev Neurosci. 2006 Oct;7(10):784-96
[6]. Minucci S, et al. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer.Nat Rev Cancer. 2006 Jan;6(1):38-51.

HDAC Isoform Comparison

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