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-16914
    MC1568
    		Inhibitor
    MC1568 is a selective class II (IIa) histone deacetylas (HDAC II) inhibitor, used for cancer research.
    MC1568
  • HY-14842B
    Givinostat hydrochloride monohydrate
    		Inhibitor ≥98.0%
    Givinostat hydrochloride monohydrate (ITF-2357 hydrochloride monohydrate) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively.
    Givinostat hydrochloride monohydrate
  • HY-153392
    TYA-018
    		Inhibitor 98.71%
    TYA-018 is an orally active, potent and highly selective HDAC6 inhibitor. TYA-018 can protect heart function in mice. TYA-018 also enhances energetics in mice by increasing expression of targets associated with fatty acid metabolism, protein metabolism, and oxidative phosphorylation.
    TYA-018
  • HY-111342
    HDAC8-IN-1
    		Inhibitor 99.82%
    HDAC8-IN-1 is a HDAC8 inhibitor with an IC50 of 27.2 nM.
    HDAC8-IN-1
  • HY-115475
    SW-100
    		Inhibitor 99.93%
    SW-100, a selective histone deacetylase 6 (HDAC6) inhibitor with an IC50 of 2.3 nM, shows at least 1000-fold selectivity for HDAC6 relative to all other HDAC isozymes. SW-100 displays a significantly improved ability to cross the blood-brain-barrier.
    SW-100
  • HY-N0071
    Crotonoside
    		Inhibitor 99.64%
    Crotonoside is isolated from Chinese medicinal herb, Croton. Crotonoside inhibits FLT3 and HDAC3/6, exhibits selective inhibition in acute myeloid leukemia (AML) cells. Crotonoside could be a promising new lead compound for the research of AML.
    Crotonoside
  • HY-16012A
    Domatinostat
    		Inhibitor 99.43%
    Domatinostat (4SC-202 free base) is a selective class I HDAC inhibitor with IC50 of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. It also displays inhibitory activity against Lysine specific demethylase 1 (LSD1).
    Domatinostat
  • 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-119939
    CHDI-390576
    		Inhibitor 98.07%
    CHDI-390576, a potent, cell permeable and CNS penetrant class IIa histone deacetylase (HDAC) inhibitor with IC50s of 54 nM, 60 nM, 31 nM, 50 nM for class IIa HDAC4, HDAC5, HDAC7, HDAC9, respectively, shows >500-fold selectivity over class I HDACs (1, 2, 3) and ~150-fold selectivity over HDAC8 and the class IIb HDAC6 isoform.
    CHDI-390576
  • HY-13265
    AR-42
    		98.69%
    AR-42 (HDAC-42; OSU-HDAC42) is a potent, orally bioavailable pan-HDAC inhibitor (IC50=16 nM). AR-42 induces growth inhibition, cell-cycle arrest, apoptosis, and activation of caspases-3/7. AR-42 promotes hyperacetylation of H3, H4, and alpha-tubulin, and up-regulation of p21. AR-42 shows cytotoxicity against various human cancer cell lines.
    AR-42
  • HY-112719
    BRD 4354
    		Inhibitor 99.66%
    BRD 4354 is a moderately potent inhibitor of HDAC5 and HDAC9, with IC50s of 0.85 and 1.88 μM, respectively.
    BRD 4354
  • HY-13432
    Nanatinostat
    		Inhibitor 99.34%
    Nanatinostat (CHR-3996) is a potent, class I selective and orally active histone deacetylase (HDAC) inhibitor with an IC50 of 8 nM.
    Nanatinostat
  • HY-144315
    CYD19
    		Inhibitor
    CYD19 is a potent Snail/HDAC dual target inhibitor. CYD19 displays potent inhibitory activity against HDAC1 with an IC50 of 0.405 μM and potent inhibition against Snail with a Kd of 0.18 μM. CYD19 increases histone H4 acetylation in HCT-116 cells and decreases the expression of Snail protein to induce cell apoptosis.
    CYD19
  • HY-153358
    TNG260
    		Inhibitor 99.91%
    TNG260 is a CoREST-selective deacetylase (CoreDAC) inhibitor. TNG260 inhibits HDAC1 with 10-fold selectivity over HDAC3. TNG260 leads to HDAC1 inhibition, reverses anti-PD1 resistance driven by loss of STK11. TNG260 decreases intratumoral infiltration of neutrophils. TNG260 exhibits immune-mediated cell killing.
    TNG260
  • HY-111400
    SR-4370
    		Inhibitor 99.95%
    SR-4370 is an inhibitor of HDAC, with IC50s of 0.13 μM, 0.58 μM, 0.006 μM, 2.3 μM, and 3.4 μM for HDAC1, HDAC2, HDAC3, HDAC8, and HDAC6, respectively.
    SR-4370
  • HY-138159
    Boc-Lys(Ac)-AMC
    		99.53%
    Boc-Lys(Ac)-AMC is a cell-permeable fluorometric HDAC substrate (Ex/Em = 355 nm/460 nm).
    Boc-Lys(Ac)-AMC
  • HY-151590
    DKFZ-748
    		Inhibitor ≥98.0%
    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-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
    		99.84%
    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
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.