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

HDAC (组蛋白去乙酰化酶)

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 亚型特异性产品:

  • HDAC

  • HDAC1

  • HDAC2

  • HDAC3

  • HDAC4

  • HDAC5

  • HDAC6

  • HDAC7

  • HDAC8

  • HDAC9

  • HDAC10

  • HDAC11

  • HD1

  • HD2

目录号 产品名 作用方式 纯度
  • HY-15144
    Trichostatin A

    曲古抑菌素A

    Inhibitor ≥98.0%
    Trichostatin A (TSA) 是有效的,特异的组蛋白去乙酰化酶类型 I 和 II (HDAC class I/II) 抑制剂,对 HDAC 的 IC50 值为 1.8 nM。
  • HY-10221
    Vorinostat

    伏立诺他

    Inhibitor
    Vorinostat (SAHA) 是一种有效的,可口服的 HDAC1HDAC2HDAC3 (Class I)HDAC6HDAC7 (Class II)Class IV (HDAC11) 的抑制剂,对 HDAC1/3 的 ID50 值分别为 10 nM 和 20 nM。Vorinostat 可以诱导细胞凋亡 (apoptosis)。Vorinostat 还是一种人类乳头瘤病毒 (HPV)-18 DNA 扩增的有效抑制剂。
  • HY-A0281
    4-Phenylbutyric acid

    4-苯基丁酸

    Inhibitor ≥98.0%
    4-Phenylbutyric acid (4-PBA) 是一种组蛋白去乙酰化酶 (HDAC) 和内质网应激 (ER) 抑制剂,可用于癌症和感染等疾病的研究。
  • HY-10585
    Valproic acid

    丙戊酸

    Inhibitor ≥98.0%
    Valproic acid (VPA; 2-Propylpentanoic Acid) 是一种 HDAC 抑制剂,IC50 值为 0.5-2 mM,抑制 HDAC1 的活性,(IC50,400 μM),同时可诱导 HDAC2 的降解。Valproic acid 激活 Notch1 信号并抑制小细胞肺癌 (SCLC) 细胞的增殖。Valproic acid 可用于癫痫、双相情感障碍和偏头痛等的研究。
  • HY-10224
    Panobinostat

    帕比司他

    Inhibitor ≥98.0%
    Panobinostat (LBH589; NVP-LBH589) 是一种有效的口服非选择性 HDAC 抑制剂,具有抗肿瘤活性。Panobinostat 可诱导 HIV-1 virus 的产生,即使在较低的浓度范围 8-31 nM,也可刺激 HIV-1 在潜伏感染细胞中的表达。Panobinostat 诱导细胞凋亡 (apoptosis) 和自噬 (autophagy)。Panobinostat 可用于难治性或复发性多发性骨髓瘤的研究。
  • HY-16138A
    Ivaltinostat formic Inhibitor 99.36%
    Ivaltinostat (CG-200745) formic 是一种口服有效的泛 HDAC 抑制剂,具有异羟肟酸部分,可在催化袋底部结合锌。Ivaltinostat formic 抑制组蛋白 H3 和微管蛋白的脱乙酰作用。Ivaltinostat formic 诱导 p53 的积累,促进 p53 依赖性反式激活,并增强 MDM2 和 p21 (Waf1/Cip1) 蛋白的表达。Ivaltinostat formic 可增强 Gemcitabine 耐药细胞对 Gemcitabine (HY-16138) 和 5-Fluorouracil (5-FU; HY-90006) 的敏感性。Ivaltinostat formic 诱导凋亡并具有抗肿瘤作用。
  • HY-145757
    Elevenostat Inhibitor
    Elevenostat (JB3-22) 是一种选择性 HDAC11 抑制剂 (IC50=0.235 µM)。抗多发性骨髓瘤 (MM) 活性。
  • HY-120448A
    QTX125 TFA Inhibitor
    QTX125 TFA 是一种有效且高度选择性的 HDAC6 抑制剂。与其他 HDAC 相比,QTX125 对 HDAC6 具有出色的选择性。QTX125 TFA 具有抗肿瘤作用。
  • HY-13755
    Sulforaphane

    萝卜硫素

    Inhibitor ≥98.0%
    Sulforaphane 是存在于多种蔬菜中的天然异硫氰酸酯。Sulforaphane 增加肿瘤抑制蛋白的转录并抑制组蛋白脱乙酰酶的活性。Sulforaphan 可以激活 Nrf2 ,并通过 AMPK 依赖性信号传导抑制高糖诱导的胰腺癌。 Sulforaphan 具有抗癌和抗炎活性。
  • HY-12163
    Entinostat

    恩替诺特

    Inhibitor 99.65%
    Entinostat 选择性,可口服的 HDAC class I 抑制剂,抑制 HDAC1HDAC2HDAC3IC50 分别为 243 nM,453 nM 和 248 nM。
  • HY-15149
    Romidepsin

    罗米地辛

    Inhibitor 99.98%
    Romidepsin (FK 228) 是具有抗肿瘤活性的组蛋白去乙酰化酶 (HDAC) 抑制剂,抑制 HDAC1,HDAC2,HDAC4 和 HDAC6,IC50 值分别为 36 nM,47 nM,510 nM 和 1.4 μM。Romidepsin (FK 228) 由紫色杆菌产生,诱导 G2/M 细胞周期阻滞和凋亡 (apoptosis)。
  • HY-109015
    Tucidinostat

    西达本胺

    Inhibitor ≥98.0%
    Tucidinostat (Chidamide) 是一种有效的,可口服的 HDAC 第 I 类 HDAC1/2/3 和第 IIb 类 HDAC10 的抑制剂,IC50 值分别为 95,160,67 和 78 nM,对 HDAC8 和 HDAC11 的作用较弱 (IC50,733 nM,432 nM),对 HDAC4/5/6/7/9 无作用。
  • HY-10585A
    Valproic acid sodium

    丙戊酸钠

    Inhibitor ≥98.0%
    Valproic acid sodium salt (Sodium Valproate) 是一种 HDAC 抑制剂,IC50 值为 0.5-2 mM,抑制 HDAC1 的活性,(IC50,400 μM),同时可诱导 HDAC2 的降解。Valproic acid sodium salt 激活 Notch1 信号并抑制小细胞肺癌 (SCLC) 细胞的增殖。Valproic acid sodium salt 可用于癫痫、双相情感障碍和偏头痛等的研究。
  • HY-13909
    RGFP966 Inhibitor 99.81%
    RGFP966 是高选择性的 HDAC3 抑制剂,IC50 为 80 nM,在 15 μM 时对其他 HDAC 无抑制作用。RGFP966 能够透过血脑屏障 (BBB)。
  • HY-16026
    Ricolinostat Inhibitor
    Ricolinostat (ACY-1215) 是一种有效,选择性的 HDAC6 抑制剂,IC50 为 5 nM。ACY-1215 也可抑制 HDAC1HDAC2HDAC3IC50 分别为 58,48 和 51 nM。
  • HY-15654
    Sodium 4-phenylbutyrate

    苯丁酸钠

    Inhibitor 99.96%
    Sodium 4-phenylbutyrate (4-PBA sodium) 是一种组蛋白去乙酰化酶 (HDAC) 和内质网应激 (ERS) 抑制剂,可用于癌症和感染等疾病的研究。
  • HY-10225
    Belinostat

    贝利司他

    Inhibitor 99.94%
    Belinostat (PXD101; PX105684) 是一种有效的 HDAC 抑制剂,在 HeLa 细胞提取物中的 IC50 为 27 nM。
  • HY-13271A
    Tubastatin A Inhibitor ≥98.0%
    Tubastatin A 是一种有效的,选择性的 HDAC6 抑制剂,IC50 值为 15 nM,对其选择性是对 HDAC8 的 57 倍多,是其他同工酶的 1000 多倍。
  • HY-10528
    Tasquinimod

    他喹莫德

    Modulator
    Tasquinimod是一种口服抗血管生成剂,有潜力用于去势抵抗性前列腺癌的研究。Tasquinimod与 HDAC4 Zn2+ 结合结构域结合的Kd 值为10-30 nM。Tasquinimod 也是一种 S100A9 抑制剂。
  • HY-12164
    Mocetinostat Inhibitor 99.43%
    Mocetinostat (MGCD0103)是一种有效,可口服和同种型选择性的 HDAC (Class I/IV) 抑制剂,抑制HDAC1HDAC2HDAC3HDAC11IC50分别为0.15,0.29,1.66 和 0.59 μM。 Mocetinostat对HDAC4,HDAC5,HDAC6,HDAC7或HDAC8没有抑制作用。

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.

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