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

HDAC

Histone deacetylases

HDAC

Related Products

PDF 2.58 MB

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-N11692
    9-Hydroxyoctadecanoic acid
    		Inhibitor ≥98.0%
    9-Hydroxyoctadecanoic acid (9-HSA) is an HDAC1 inhibitor that inhibits ∼66.4% HDAC1 enzymatic activity at 5 μM. 9-Hydroxyoctadecanoic acid shows anticancer activity.
    9-Hydroxyoctadecanoic acid
  • HY-144779
    HDAC10-IN-1
    		Inhibitor 99.11%
    HDAC10-IN-1 (compound 13b) is a potent and highly selective HDAC10 inhibitor, with an IC50 of 58 nM. HDAC10-IN-1 modulates autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells.
    HDAC10-IN-1
  • HY-132998
    HDAC6 degrader-1
    		Degrader 98.59%
    HDAC6 degrader-1 (Compound NP8) is the PROTAC degrader for HDAC6 with a DC50 of 3.8 nM in cell MM.1S.(Blue: ligand for E3 ligase Pomalidomide (HY-10984); Black: linker (HY-140213); Pink: ligand for target protein Nexturastat A (HY-16699))
    HDAC6 degrader-1
  • HY-104008
    ACY-957
    		Inhibitor 99.66%
    ACY-957 is an orally active and selective inhibitor of HDAC1 and HDAC2, with IC50s of 7 nM, 18 nM, and 1300 nM against HDAC1/2/3, respectively, and shows no inhibition on HDAC4/5/6/7/8/9.
    ACY-957
  • HY-151590
    DKFZ-748
    		Inhibitor 98.01%
    DKFZ-748 is a selective HDAC10 inhibitor (pIC50=7.66), and shows anti-tumor activity.
    DKFZ-748
  • HY-138799
    KA2507
    		Inhibitor 99.24%
    KA2507 is a potent, orally active and selective HDAC6 inhibitor, with an IC50 of 2.5 nM. KA2507 shows antitumor activities and immune modulatory effects in preclinical models.
    KA2507
  • HY-123295
    HDAC3-IN-T247
    		Inhibitor 98.91%
    HDAC3-IN-T247 is a potent and selective HDAC3 (histone deacetylase 3) inhibitor, with an IC50 of 0.24 µM. HDAC3-IN-T247 induces a selective increase of NF-κB acetylation in HCT116 cells. HDAC3-IN-T247 shows anticancer and antiviral activity. HDAC3-IN-T247 inhibits growth of cancer cells, and activates HIV gene expression in latent HIV-infected cells.
    HDAC3-IN-T247
  • HY-101780
    Tinostamustine
    		Inhibitor 99.64%
    Tinostamustine (EDO-S101) is a pan HDAC inhibitor; inhibits HDAC6, HDAC1, HDAC2 and HDAC3 with IC50 values of 6 nM, 9 nM, 9 nM and 25 nM, respectively.
    Tinostamustine
  • HY-126147
    J22352
    		Inhibitor 99.04%
    J22352 is a PROTAC (proteolysis-targeting chimeras)-like and highly selective HDAC6 inhibitor with an IC50 value of 4.7 nM. J22352 promotes HDAC6 degradation and induces anticancer effects by inhibiting autophagy and eliciting the antitumor immune response in glioblastoma cancers, and leading to the restoration of host antitumor activity by reducing the immunosuppressive activity of PD-L1.
    J22352
  • HY-143248
    KR-39038
    		Inhibitor 99.48%
    KR-39038 is an orally active and potent GRK5 (G protein-coupled receptor kinase 5) inhibitor, with an IC50 of 0.02 μM. KR-39038 significantly inhibits angiotensin II-induced cellular hypertrophy through suppression of HDAC5 pathway in neonatal cardiomyocytes. KR-39038 shows profound anti-hypertrophic effects and improved cardiac function. KR-39038 can be used for heart failure research.
    KR-39038
  • HY-18976
    UF010
    		99.83%
    UF010 is a selective inhibitor of class I HDAC. UF010 has cytotoxicity to cancer cells and reduces neuroinflammation in the hippocampus. UF010 can be used for the research of neurological diseases.
    UF010
  • HY-161307
    T-518
    		Inhibitor 98.40%
    T-518 is an orally active, BBB-penetrant and potent DFMO-based HDAC6 inhibitor with high selectivity (IC50 = 36 nM). T-518 improves axonal transport. T-518 ameliorates object recognition deficit. T-518 can be studied in research for Alzheimer’s disease and tauopathy.
    T-518
  • HY-19350
    BML-210
    		Inhibitor 98.04%
    BML-210 is a potent HDAC inhibitor. BML-210 can inhibit the HDAC4-VP16-driven reporter signal with an apparent IC50 of ∼5 µM. BML-210 has a specific disruptive effect on the HDAC4:MEF2 interaction. BML-210 causes an increase in the G0/G1 phase. BML-210 induces apoptosis and displays antitumour activities in orthotopic mammary tumours in mice.
    BML-210
  • HY-161305
    SE-7552
    		Inhibitor 99.48%
    SE-7552, a 2-(difluoromethyl)-1,3,4-oxadiazole (DFMO) derivative, is an orally active, highly selective, non-hydroxamate HDAC6 inhibitor with an IC50 of 33 nM. SE-7552 is greater than 850-fold selectivity versus all other known HDAC isozymes. SE-7552 is capable of blocking multiple myeloma growth in vivo. SE-7552 acts as an anti-obesity agent in diet-induced obese mice.
    SE-7552
  • HY-19348
    Pimelic Diphenylamide 106
    		Inhibitor 98.54%
    Pimelic Diphenylamide 106 (TC-H 106) is a slow, tight binding class I HDAC inhibitor (inhibits HDAC1, 2, and 3 with IC50 values of 150 nM, 760 nM, and 370 nM, respectively), with no activity against class II HDACs. Pimelic Diphenylamide 106 modulates dopamine concentration and protects dopamine cells by inducing VMAT2 expression. Pimelic Diphenylamide 106 can be used in the study of neuropsychiatric diseases such as attention deficit hyperactivity disorder (ADHD).
    Pimelic Diphenylamide 106
  • HY-126330
    SS-208
    		Inhibitor 99.00%
    SS-208 is a selective HDAC6 inhibitor, with an IC50 of 12 nM. SS-208 possesses anti-tumor activity in melanoma.
    SS-208
  • HY-126052
    Gnetol
    		Inhibitor 99.86%
    Gnetol is a phenolic compound isolated from the root of Gnetum montanum . Gnetol potently inhibits COX-1 (IC50 of 0.78 μM) and HDAC. Gnetol is a potent tyrosinase inhibitor with an IC50 of 4.5 μM for murine tyrosinase and suppresses melanin biosynthesis. Gnetol has antioxidant, antiproliferative, anticancer and hepatoprotective activity. Gnetol also possesses concentration-dependent α-Amylase, α-glucosidase, and adipogenesis activities.
    Gnetol
  • HY-13267
    Droxinostat
    		Inhibitor 98.91%
    Droxinostat (NS 41080) is a histone deacetylase (HDAC) inhibitor. Droxinostat selectively inhibits HDAC3, HDAC6, and HDAC8 with IC50 values of 16.9 μM, 2.47 μM, and 1.46 μM, respectively. Droxinostat can be used for the research of hepatocellular carcinoma (HCC).
    Droxinostat
  • HY-100871
    WT-161
    		Inhibitor 98.36%
    WT-161 is a potent and selective HDAC6 inhibitor with an IC50 of 0.40 nM. WT-161 also inhibits metallo-β-lactamase domain-containing protein 2 (MBLAC2).
    WT-161
  • HY-114414
    HDACs/mTOR Inhibitor 1
    		Inhibitor 99.01%
    HDACs/mTOR Inhibitor 1 is a dual HDAC.html" class="link-product" target="_blank">HDACs and mTOR.html" class="link-product" target="_blank">mTOR inhibitor, with IC50s of 0.19 nM, 1.8 nM, 1.2 nM for HDAC1, HDAC6, mTOR, respectively. HDACs/mTOR Inhibitor 1 stimulates cell cycle arrest in G0/G1 phase and induces tumor cell apoptosis with low toxicity in vivo. HDACs/mTOR Inhibitor 1 can be used in the research of hematologic malignancies.
    HDACs/mTOR Inhibitor 1
Cat. No. Product Name / Synonyms Application Reactivity
All Rights Reserved.
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

Your Search Returned No Results.

Sorry. There is currently no product that acts on isoform together.

Please try each isoform separately.