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-100384
    NKL 22
    		Inhibitor
    NKL 22 (compound 4b) is a potent and selective inhibitor of histone deacetylases (HDAC), with an IC50 of 199 and 69 nM for HDAC1 and HDAC3, respectively. NKL 22 exhibits selectivity over HDAC2/4/5/7/8 (IC50≥1.59 μM). NKL 22 ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice.
    NKL 22
  • HY-109109
    Alteminostat
    		Inhibitor 98.66%
    Alteminostat (CKD-581) is a potent HDAC inhibitor. Alteminostat inhibits the class I-II HDAC family via histone H3 and tubulin acetylation. Alteminostat can be used for lymphoma and multiple myeloma research.
    Alteminostat
  • HY-124295
    Imofinostat
    		Inhibitor 99.40%
    Imofinostat (ABT-301; MPT0E028) is an orally active and selective HDAC inhibitor with IC50s of 53.0 nM, 106.2 nM, 29.5 nM for HDAC1, HDAC2 and HDAC6, respectively. Imofinostat has a weak inhibitory effect on HDAC8 (IC50 of 2.5 ​​μM), but no inhibitory effect on HDAC4 (IC50>10 μM). Imofinostat reduces the viability of B-cell lymphomas by inducing apoptosis and possesses potent direct Akt targeting ability and reduces Akt phosphorylation in B-cell lymphoma. Imofinostat has a broad-spectrum antitumor activity, including colorectal cancer, B-cell lymphoma, non-small cell lung carcinoma (NSCLC), and pancreatic cancer, while also showing therapeutic potential in non-tumor diseases like emphysema and pulmonary fibrosis.
    Imofinostat
  • HY-114483
    AES-135
    		Inhibitor 98.21%
    AES-135, a hydroxamic acid-based pan-HDAC inhibitor, prolongs survival in an orthotopic mouse model of pancreatic cancer. AES-135 inhibits HDAC3, HDAC6, HDAC8, and HDAC11 with IC50s ranging from 190-1100 nM.
    AES-135
  • HY-A0281S
    4-Phenylbutyric acid-d11
    		Inhibitor 99.30%
    4-Phenylbutyric acid-d11 is the deuterium labeled 4-Phenylbutyric acid. 4-Phenylbutyric acid (4-PBA) is an inhibitor of HDAC and endoplasmic reticulum (ER) stress, used in cancer and infection research.
    4-Phenylbutyric acid-d<sub>11</sub>
  • HY-10585S1
    Valproic acid-d6
    		Inhibitor 99.83%
    Valproic acid-d6 is the deuterium labeled Valproic acid. Valproic acid (VPA; 2-Propylpentanoic Acid) is an 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 activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid sodium salt is used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches.
    Valproic acid-d<sub>6</sub>
  • HY-12954
    PTACH
    		Inhibitor 99.65%
    PTACH (NCH-51) is a potent HDAC inhibitor with IC50s of 48 nM, 32 nM, and 41 nM for HDAC1, HDAC4, and HDAC6, respectively. PTACH exerts potent growth inhibition against various cancer cells (EC50s of 1.1-9.1 μM) .
    PTACH
  • HY-174444A
    PROTAC HDAC degrader-2 TFA
    		Degrader
    PROTAC HDAC degrader-2 TFA is the trifluoroacetate salt of PROTAC HDAC degrader-2. PROTAC HDAC degrader-2 is a selective IIb HDACs PROTAC degrader, with DC50s of 13 nM for HDAC6, 29 nM for HDAC10, respectively. PROTAC HDAC degrader-2 exhibits low cytotoxicity against hematological and solid cancer cell lines. PROTAC HDAC degrader-2 can be used for the chemical knockdown of class IIb HDACs. ( Pink: HDAC ligand : (HY-174471), Blue: E3 ligase CRBN Ligand (HY-131717), E3 ligase ligand-linker conjugate (HY-174473)).
    PROTAC HDAC degrader-2 TFA
  • HY-145259
    HDAC6-IN-3
    		Inhibitor 98.0%
    HDAC6-IN-3 (Compound 14), an antiprostate cancer agent, is a potent, orally active HDAC6 inhibitor with IC50s ranging from 0.02-1.54 μM for HDAC1/2/3/6/8/10. HDAC6-IN-3 is also an effective MAO-A (IC50=0.79 μM) and LSD1 inhibitor. HDAC6-IN-3 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    HDAC6-IN-3
  • HY-155697
    SGC-UBD253
    		Antagonist 99.3%
    SGC-UBD253, a chemical probe, is a potent HDAC6-UBD antagonist. SGC-UBD253 can be used in research of cancer.
    SGC-UBD253
  • HY-130538
    1-Naphthohydroxamic acid
    		Inhibitor 99.59%
    1-Naphthohydroxamic acid (Compound 2) is a potent and selective HDAC8 inhibitor with an IC50 of 14 μM. 1-Naphthohydroxamic acid is more selectively for HDAC8 than class I HDAC1 and class II HDAC6 (IC50 >100 μM). 1-Naphthohydroxamic acid does not increase global histone H4 acetylation and also does not reduce total intracellular HDAC activity.1-Naphthohydroxamic acid can induce tubulin acetylation.
    1-Naphthohydroxamic acid
  • HY-162361
    HDAC1-IN-7
    		Inhibitor 99.97%
    HDAC1-IN-7 (compound 9) is potent HDAC1 inhibitor, with the IC50 of 0.957 mM.
    HDAC1-IN-7
  • HY-170495
    HDAC6 degrader-5
    		Inhibitor 99.55%
    HDAC6 degrader-5 (Compound 6) exhibits inhibitory and degradation activity against HDAC6, with an IC50 of 4.95 nM and a DC50 of 0.96 nM. HDAC6 degrader-5 inhibits the release of TNF-α, IL-1β and IL-6, blocks the hepatocyte apoptosis. HDAC6 degrader-5 exhibits anti-inflammatory activity in mouse APAP (HY-66005)-induced liver injury models.
    HDAC6 degrader-5
  • HY-10528S
    Tasquinimod-d3
    		Modulator 99.34%
    Tasquinimod-d3 (ABR-215050-d3) is the deuterium labeled Tasquinimod (HY-10528). Tasquinimod is an oral antiangiogenic agent, which plays an important role in castration-resistant prostate cancer. Tasquinimod binds to the regulatory Zn2+ binding domain of HDAC4 with Kd of 10-30 nM. Tasquinimod also is a S100A9 inhibitor.
    Tasquinimod-d<sub>3</sub>
  • HY-143412
    MIR002
    		Inhibitor 99.0%
    MIR002 is a potent and orally active DNA polymerase α (POLA1) and HDAC 11 dual inhibitor. MIR002 induces acetylation of p53, activation of p21, G1/S cell cycle arrest, and apoptosis. MIR002 shows significant antitumor activity in vivo.
    MIR002
  • HY-172157
    HDAC11-IN-2
    		Inhibitor 99.52%
    HDAC11-IN-2 (compound B6) is a high selective Histone Deacetylase 11 (HDAC11) inhibitor. HDAC11-IN-2 inhibits HDAC11 and HDAC8 with IC50s of 51.1 ×10-3 μM and 5 μM, respectively. HDAC11-IN-2 inhibits denovolipogenesis (DNL) and promotes fatty acid oxidation, thus mitigating hepaticlipid accumulation and pathological symptoms in MASLD mice. HDAC11-IN-2 enhances the phosphorylation of AMPKα1 at Thr172 through the inhibition of HDAC11, consequently modulating DNL and fatty acid oxidation in the liver.
    HDAC11-IN-2
  • HY-15654S
    Phenylbutyrate-d11 sodium
    		Inhibitor 99.85%
    Phenylbutyrate-d11 (sodium) is deuterium labeled Sodium 4-phenylbutyrate. Sodium 4-phenylbutyrate (4-PBA sodium) is an inhibitor of HDAC and endoplasmic reticulum (ER) stress, used in cancer and infection research.
    Phenylbutyrate-d<sub>11</sub> sodium
  • HY-152147
    SZUH280
    		Degrader 99.38%
    SZUH280 is a potent and selective PROTAC HDAC8 degrader with a DC50 of 0.58 μM in A549 cells. SZUH280 induces cancer cell apoptosis. SZUH280 hampers DNA damage repair in cancer cells, promoting cellular radiosensitization.
    SZUH280
  • HY-143411
    GEM144
    		Inhibitor
    GEM144 is a potent and orally active DNA polymerase α (POLA1) and HDAC 11 dual inhibitor. GEM144 induces acetylation of p53, activation of p21, G1/S cell cycle arrest, and apoptosis. GEM144 has significant antitumor activity in human orthotopic malignant pleural mesothelioma xenografts.
    GEM144
  • HY-108701
    Nampt-IN-3
    		Inhibitor 98.97%
    Nampt-IN-3 (Compound 35) simultaneously inhibit nicotinamide phosphoribosyltransferase (NAMPT) and HDAC with IC50s of 31 nM and 55 nM, respectively. Nampt-IN-3 effectively induces cell apoptosis and autophagy and ultimately leads to cell death.
    Nampt-IN-3
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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