Quisinostat (JNJ-26481585) 2HCl

For research use only. Not for use in humans.

目录号:S1096

Quisinostat (JNJ-26481585) 2HCl Chemical Structure

CAS No. 875320-31-3

Quisinostat (JNJ-26481585) 2HCl是一种新型的,第二代HDAC抑制剂,对HDAC1最有效,无细胞试验中IC50为0.11 nM,作用于HDACs 2,4,10,和11适度有效;比作用于HDACs 3,5,8,和9选择性强30倍,对HDACs 6和7作用效果最弱。Phase 2。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 2691.01 现货
RMB 1726.45 现货
RMB 7921.36 现货
RMB 20229.3 现货
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客户使用Selleck生产的Quisinostat (JNJ-26481585) 2HCl发表文献45篇:

产品安全说明书

HDAC抑制剂选择性比较

生物活性

产品描述 Quisinostat (JNJ-26481585) 2HCl是一种新型的,第二代HDAC抑制剂,对HDAC1最有效,无细胞试验中IC50为0.11 nM,作用于HDACs 2,4,10,和11适度有效;比作用于HDACs 3,5,8,和9选择性强30倍,对HDACs 6和7作用效果最弱。Phase 2。
特性 JNJ-26481585是口服生物有效性的,二代氧肟酸基的HDAC抑制剂。
靶点
HDAC1 [1]
(Cell-free assay)
HDAC2 [1]
(Cell-free assay)
HDAC11 [1]
(Cell-free assay)
HDAC10 [1]
(Cell-free assay)
HDAC4 [1]
(Cell-free assay)
0.11 nM 0.33 nM 0.37 nM 0.46 nM 0.64 nM
体外研究

体外, JNJ-26481585有效抑制一组重组HDAC酶,最有效抑制HDAC1,IC50为 0.11 nM,另外抑制其他家族成员如HDAC2, 4, 10和 11时效果稍微低点,IC50分别为0.33 nM, 0.64 nM, 0.46 nM 和0.37 nM。[1] JNJ-26481585 作用于实体瘤和血癌细胞系,如肺癌,乳腺癌,结肠癌,前列腺癌,脑癌,和卵巢癌细胞系,IC50 为3.1 到 246 nM,具有广谱抗增殖活性,作用于多种人类癌细胞系时,JNJ-26481585效果比 Vorinostat, R306465, Panobinostat, CRA-24781, 和 Mocetinostat 好。[1] 最新研究显示JNJ-26481585 在低纳摩尔浓度时通过耗尽Mcl-1及诱导Hsp72产生而促进骨髓癌细胞死亡。[2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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Saos-2 NF3sWnJyUFSVIHHzd4F6 NX;6SZNbeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW2Gxcz2yJINmdGy| NYK2VHB1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2 NWTyb4d[eUiWUzDhd5NigQ>? MVLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJHNLNUeETUKgZ4VtdHN? NEG3bI89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
RD NWLxPJM5eUiWUzDhd5NigQ>? NV3RdJpXeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiT4L0bI9od26jbDCzSEB3cWGkaXzpeJkhe2O{ZXXuJIZweiCURDDj[Yxtew>? M2f5b|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
HDAC1 / HDAC2 / HDAC4; 

PubMed: 30443188     


The effects of quisinostat on the expressions of HDACs in HCC cells. The expression levels of HDAC1, HDAC2 and HDAC4 were suppressed in both HCCLM3 and SMMC-7721 cell lines. Images were photographed with confocal microscope under ×200 magnification. Scale bar, 100 μm. Data were shown as mean ± SD. n = 3; * P < 0.05, ** P < 0.01 and *** P < 0.001 compared with DMSO group.

p21 / CDK2 / CDK4 / CDK6 / Cyclin D1 / Cyclin E1 / Cyclin A2; 

PubMed: 30443188     


Western blot analysis of p21, cdk2, cdk4, cdk6, cyclinD1, cyclinE1 and cyclinA2 proteins after quisinostat treatment. 

Caspase-3/ Cleaved caspase-3 / caspase-9 / Cleaved caspase-9 / PARP / Cleaved PARP / Bcl-xl / Bcl2 / Bax / Survivin; 

PubMed: 30443188     


Western blot analysis of Caspase-3, cleaved-Caspase-3, Caspase-9, cleaved-Caspase-9, PARP, cleaved-PARP, Bcl-xl, Bcl2, Bax and survivin protein were carried out after quisinostat treatment. 

PI3K-p110 / PI3K-p85 / p-AKT / JNK / p-JNK / p-c-Jun ; 

PubMed: 30443188     


HCCLM3 and SMMC-7721 cells were treated with quisinostat (12.5, 25.0 and 50.0nM) for 48 h. Western blot analysis was used to evaluate expressions of PI3K-p110, PI3K-p85, phosphorylation of AKT473, JNK, phosphorylation of JNK and c-Jun.

30443188
Growth inhibition assay
Cell viability; 

PubMed: 30443188     


Quisinostat inhibited cell proliferation in HCCLM3, Sk-hep-1, Hep-3B, Huh7 and SMMC-7721 cells as a concentration-dependent manner verified by CCK8 assay. 

30443188
体内研究 JNJ-26481585按最大耐受剂量(10 mg/kg腹腔注射及40 mg/kg口服处理)作用于对HDAC1敏感的A2780卵巢癌模型3天,导致产生HDAC1-调节的荧光, 可测的抑制肿瘤生长效果。而且, 与5-fluorouracil/Leucovorin相比,JNJ-26481585更有效抑制C170HM2大肠癌肝转移。[1]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
- 合并

HDAC 活性实验 :

使用杆状病毒感染的Sf9细胞表达全长HDAC蛋白。此外, HDAC3共表达作为与人类NCOR2作用的复合体。为了测定含HDAC1细胞复合体活性, 免疫沉淀反应的HDAC1复合体和组蛋白H4肽段[生物素-(6-氨基)Gly-Ala-(乙酰基[3H])Lys-Arg-His-Arg-Lys-Val-NH2]的[3H]乙酰基标记的片段在50μL酶实验buffer(25mM HEPES (pH 7.4),1 M 蔗糖, 0.1 mg/mL BSA 和0.01% (v/v) Triton X-100)中温育。在37oC下温育45分钟,或者在室温下温育30分钟。加入底物之前,加入浓度不断增加的HDAC抑制剂,然后在室温下预温育10分钟。温育后,加入35μL 终止 buffer (1 M HCl 和0.4 M 乙酸)终止反应。用800μL乙酸乙酯提取释放 [3H]乙酸,然后通过闪烁计数器量化。通过Western blot 分析,测定等量的进行免疫沉淀反应的HDAC1。
细胞实验:[1]
- 合并
  • Cell lines: NCL-H2106, Colo699和 LNCAP
  • Concentrations: 0到300 nM
  • Incubation Time: 24 小时
  • Method: 使用MTT测定HDAC抑制剂抑制细胞增殖的效果。使用Alamar Blue法测定非小细胞肺癌(NSCLC)细胞系的增殖。为了测定 血癌细胞系的增殖,细胞温育72小时,通过 MTS实验测评毒性。进行三次平行实验,测定 IC50。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: 在腹股沟区皮下注射HCT116人类结肠癌细胞的雄性NMRI nu/nu无胸腺鼠, 腹腔注射溶于1 mL 0.9% NaCl(pH 7.3)的C170HM2细胞悬浮液的雄性MFI裸鼠
  • Dosages: ≤10 mg/kg
  • Administration: 口服处理或腹腔注射
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 79 mg/mL (169.02 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
2% DMSO+30% PEG 300+ddH2O
5mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 467.39
化学式

C21H28Cl2N6O2

CAS号 875320-31-3
储存条件 粉状
溶于溶剂
别名 N/A

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02948075 Completed Drug: Quisinostat|Drug: Paclitaxel|Drug: Carboplatin Ovarian Cancer NewVac LLC|Janssen Pharmaceutica N.V. Belgium September 2015 Phase 2
NCT01464112 Completed Drug: JNJ-2641585 / VELCADE / Dexamethasone Multiple Myeloma Janssen Research & Development LLC September 16 2011 Phase 1
NCT00676728 Terminated Drug: JNJ-26481585 Advanced or Refractory Leukemia|Myelodysplastic Syndromes Johnson & Johnson Pharmaceutical Research & Development L.L.C. December 2008 Phase 1
NCT00677105 Completed Drug: JNJ-26481585 Lymphoma|Neoplasms Johnson & Johnson Pharmaceutical Research & Development L.L.C.|Janssen Pharmaceutica N.V. Belgium August 2007 Phase 1

技术支持

在订购、运输、储存和使用我们的产品的任何阶段,您遇到的任何问题,均可以通过拨打我们的热线电话400-668-6834,或者技术支持邮箱tech@selleck.cn,直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1:

    I was thinking of resuspending the powder in 10% hydroxy-propyl-β-cyclodextrin, 25mg/ml mannitol, in sterile water (final pH 8.7). Is this a good vehicle to use? What is the solubility of this chemical in such a vehicle?

  • 回答:

    This vehicle can be used for in vivo studies. The following papers also used this vehicle: 1. http://www.nature.com/leu/journal/v23/n10/full/leu2009121a.html; 2. http://cancerres.aacrjournals.org/content/69/13/5307.long (The solvent contains 10% hydroxypropyl-β-cyclodextrin, 0.8% HCl (0.1 N), 0.9 % NaOH (0.1 N), 3.4% mannitol and pyrogen-free water). The solubility is 2mg/ml.

免费分装抑制剂

HDAC Signaling Pathway Map

HDAC Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID