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-149578
    Tubulin/HDAC-IN-3
    		Inhibitor
    Tubulin/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.
    Tubulin/HDAC-IN-3
  • HY-158371
    HDAC/CK2-IN-1
    		Inhibitor
    HDAC/CK2-IN-1 (compound 38) is a HDAC1 (IC50 = 1.46 μM), HDAC6 (IC50 = 0.66 μM), and CK2 (IC50 = 3.67 μM) inhibitor. HDAC/CK2-IN-1 exhibits promising antproliferative activity against Jurkat, MCF-7, HCT-116, and HL-60 cell lines.
    HDAC/CK2-IN-1
  • HY-139796
    ZYJ-34v
    		Inhibitor
    ZYJ-34v is an orally active histone deacetylase inhibitor. ZYJ-34v has antitumor activity.
    ZYJ-34v
  • HY-155396
    PRO-HD1
    		Degrader
    PRO-HD1 is a PROTAC HDAC6 degrader. PRO-HD1 degrades HDAC6 in A549 cells, and inhibits proliferation of Jurkat cells (IC50: 5.8 μM).
    PRO-HD1
  • HY-143241
    HDAC-IN-34
    		Inhibitor
    HDAC-IN-34 (compound 27) is a potent HDAC inhibitor, with IC50 values of 0.022 and 0.45 μM for HDAC1 and HDAC6, respectively. HDAC-IN-34 can bind to DNA and cause DNA damage. HDAC-IN-34 causes cells apoptosis through p53 signaling pathway. HDAC-IN-34 exhibits significant anti-proliferation effect against HCT-116 cells, with an IC50 of 1.41 μM.
    HDAC-IN-34
  • HY-10221G
    Vorinostat (GMP)
    		Inhibitor
    Vorinostat (GMP) is a GMP grade Vorinosta (HY-10221). GMP-grade small molecules can be used as auxiliary agents in cell therapy. Vorinostat is a potent, orally available HDAC1, HDAC2, HDAC3 (Class I), HDAC6 and Inhibitors of HDAC7 (Class II) and Class IV (HDAC11).
    Vorinostat (GMP)
  • HY-W769286
    Valproic acid β-D-glucuronide-d15
    Valproic acid β-D-glucuronide-d15 is the deuterium labeled Valproic acid β-D-glucuronide (HY-W400496). Valproic acid β-D-glucuronide is the major urinary metabolite of Valproic acid (HY-10585).
    Valproic acid β-D-glucuronide-d<sub>15</sub>
  • HY-143325
    A2AAR/HDAC-IN-2
    		Inhibitor
    A2AAR/HDAC-IN-2 is a potent A2AAR/HDAC dual inhibitor, with good binding affinity for A2AAR (Ki=10.3 nM) and good inhibitory activity against HDAC1 (IC50=18.5 nM). A2AAR/HDAC-IN-2 can be used in study of antitumor.
    A2AAR/HDAC-IN-2
  • HY-151897
    HDAC-IN-49
    		Inhibitor
    HDAC-IN-49 is a potent unselective HDAC (HDAC) inhibitor with IC50s of 13 nM, 14 nM, 21 nM, 1880 nM, and 10 nM for HDAC1, HDAC2, HDAC3, HDAC4, and HDAC6. HDAC-IN-49 demonstrates prominent antileukemic activity with low cytotoxic activity toward healthy cells.
    HDAC-IN-49
  • HY-151153
    HDAC1-IN-5
    		Inhibitor
    HDAC1-IN-5 is a potent HDAC1 inhibitor with IC50 values of 15 nM and 20 nM for HDAC1 and HDAC6, respectively. HDAC1-IN-5 can enhance the acetylation of histone H3 and α-tubulin, as well as promote the activation of caspase 3 in cancer cells, thereby inducing apoptosis. HDAC1-IN-5 induces chromatin damage by binding with DNA. HDAC1-IN-5 has strong inhibitory activity against tumor growth in xenograft mice.
    HDAC1-IN-5
  • HY-174265
    HDAC6-IN-60
    		Inhibitor
    HDAC6-IN-60 (Compound 12) is an orally active and selective HDAC6 inhibitor. HDAC6-IN-60 exerts effects on tumor cell proliferation by inhibiting the enzymatic activity of HDAC6 and regulating pathways related to protein homeostasis. HDAC6-IN-60 is promising for research of HDAC6- related cancers.
    HDAC6-IN-60
  • HY-178487
    anti-TNBC agent-12
    		Inhibitor
    anti-TNBC agent-12 (Compound 23a) is a multi-target antitumor agent targeting HDAC6 (IC50=30.3 nM), DNA, and inducing nitric oxide (NO) release. anti-TNBC agent-12 induces tumor cell apoptosis and G2/M phase cell cycle arrest. anti-TNBC agent-12 is promising for research of triple-negative breast cancer (TNBC).
    anti-TNBC agent-12
  • HY-157401
    HDAC6-IN-29
    		Inhibitor
    HDAC6-IN-29 (compound 11g), hydroxamic analogue, is a HDAC6 inhibitor. HDAC6-IN-29 has potent antiproliferative activity against CAL-51 cells (IC50 = 1.17 μM) and is able to induce apoptosis and cause accumulation of cells in the S phase of the cell cycle. HDAC6-IN-29 can be used for the research of cancer.
    HDAC6-IN-29
  • HY-174149
    HDAC6-IN-59
    		Inhibitor
    HDAC6-IN-59 (Compound 38k) is a highly selective histone deacetylase 6 (HDAC6) inhibitor (IC50=3.12 nM, with 352-fold selectivity over HDAC1). HDAC6-IN-59 is promising for research of esophageal cancer.
    HDAC6-IN-59
  • HY-145688
    HDAC-IN-33
    		Inhibitor
    HDAC-IN-33 is a potent HDAC inhibitor with IC50s of 24, 46, and 47 nM for HDAC1, HDAC2 and HDAC6, respectively. HDAC-IN-33 possesses potent antiproliferation activities against tumor cells. HDAC-IN-33 shows potent antitumor efficacy in vivo That trigger antitumor immunity.
    HDAC-IN-33
  • HY-161524
    HDAC6-IN-43
    		Inhibitor
    HDAC6-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).
    HDAC6-IN-43
  • HY-178104
    HDAC-IN-93
    		Inhibitor
    HDAC-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.
    HDAC-IN-93
  • HY-172889
    PI3K/HDAC-IN-4
    		Inhibitor
    PI3K/HDAC-IN-4 (Compound 31f) is a PI3K/HDAC dual inhibitor (IC50: 0.2μM). PI3K/HDAC-IN-4 shows high selectivity for HDAC1-3 (IC50 values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively). PI3K/HDAC-IN-4 is a potent PIK3 inhibitor with IC50 values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. PI3K/HDAC-IN-4 significantly induces tumor cell apoptosis by simultaneously inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. PI3K/HDAC-IN-4 exhibits potent antiproliferative activity in a variety of tumor cell lines (e.g., MV4-11, Jeko-1, HL60, and MCF-7, with IC50 values of 0.2, 0.9, 0.8, and 1.5 μM, respectively). PI3K/HDAC-IN-4 can be used in the study of lymphoma and leukemia.
    PI3K/HDAC-IN-4
  • HY-170379
    HDAC-IN-84
    		Inhibitor
    HDAC-IN-84 (compound 4d) is a potent HDAC inhibitor, with IC50 values of 0.0045, 0.015, 0.013, 0.038, 5.8 and 26 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8 and HDAC11, respectively. HDAC-IN-84 effectively inhibits the proliferation of leukemia cells without causing toxicity.
    HDAC-IN-84
  • HY-174401
    PROTAC HDAC6 degrader 5
    		Inhibitor
    PROTAC HDAC6 degrader 5 (Compound 5a) is a highly selective PROTAC targeting HDAC6. PROTAC HDAC6 degrader 5 can effectively degrade HDAC6 in cells (IC50 = 43 nM). PROTAC HDAC6 degrader 5 reduces HDAC6 levels through proteasome- and CRBN-dependent mechanisms (Pink: Target protein ligand (HY-174408), Target protein ligand + linker (HY-174409); Blue: Pomalidomide (HY-10984), Pomalidomide 4'-alkylC3-azide (HY-139341)).
    PROTAC HDAC6 degrader 5
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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