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1012054-59-9 分子结构
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7-({4-[(3-ethynylphenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-N-hydroxyheptanamide

ChemBase编号:72571
分子式:C24H26N4O4
平均质量:434.48764
单一同位素质量:434.19540533
SMILES和InChIs

SMILES:
c12c(ncnc1Nc1cc(ccc1)C#C)cc(c(c2)OCCCCCCC(=O)NO)OC
Canonical SMILES:
ONC(=O)CCCCCCOc1cc2c(ncnc2cc1OC)Nc1cccc(c1)C#C
InChI:
InChI=1S/C24H26N4O4/c1-3-17-9-8-10-18(13-17)27-24-19-14-22(21(31-2)15-20(19)25-16-26-24)32-12-7-5-4-6-11-23(29)28-30/h1,8-10,13-16,30H,4-7,11-12H2,2H3,(H,28,29)(H,25,26,27)
InChIKey:
PLIVFNIUGLLCEK-UHFFFAOYSA-N

引用这个纪录

CBID:72571 http://www.chembase.cn/molecule-72571.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
7-({4-[(3-ethynylphenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-N-hydroxyheptanamide
IUPAC传统名
7-({4-[(3-ethynylphenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-N-hydroxyheptanamide
别名
7-[[4-[(3-Ethynylphenyl)amino]-7-methoxy-6-quinazolinyl]oxy]-N-hydroxyheptanamide
7-[[4-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-yl]oxy]-N-hydroxyheptanamide
CUDC-101
CAS号
1012054-59-9
PubChem SID
162037496
PubChem CID
24756910

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID
PubChem 24756910 external link

理论计算性质

理论计算性质

JChem
Acid pKa 8.90756  质子受体
质子供体 LogD (pH = 5.5) 3.7691047 
LogD (pH = 7.4) 3.80824  Log P 3.8221774 
摩尔折射率 118.6277 cm3 极化性 47.2623 Å3
极化表面积 105.6 Å2 可自由旋转的化学键 11 
里宾斯基五规则 true 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
DMSO expand 查看数据来源
保存条件
-20°C expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
作用靶点
EGFR expand 查看数据来源
HDAC expand 查看数据来源
HER2 expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
质检报告
下载链接 expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals TRC TRC
Selleck Chemicals -  S1194 external link
Research Area
Description Breast cancer,Gastric cancer, Head&neck cancer
Biological Activity
Description CUDC-101 is a potent multi-target inhibitor targeting HDAC, EGFR and HER2 with IC50 of 4.4 nM, 2.4 nM, and 15.7 nM, respectively.
Targets HDAC EGFR HER2
IC50 4.4 nM 2.4 nM 15.7 nM [1]
In Vitro Specific for class I and class II HDACs, CUDC-101 does not inhibit class III Sir-type HDACs. CUDC-101 displays weak activity against other protein kinases including KDR/VEGFR2, Lyn, Lck, Abl-1, FGFR-2, Flt-3, and Ret with IC50 of 0.85 μM, 0.84 μM, 5.91 μM, 2.89 μM, 3.43 μM, 1.5 μM, abd 3.2 μM, respectively. CUDC-101 displays broad antiproliferative activity in many human cancer cell types with IC50 of 0.04-0.80 μM, exhibiting a higher potency than erlotinib, lapatinib, and combinations of vorinostat with either erlotinib or lapatinib in most cases. CUDC-101 potently inhibits lapatinib- and erlotinib-resistant cancer cell lines. [1] CUDC-101 inhibits the erlotinib-resistant EGFR mutant T790M although its effects are incomplete with an Amax of ~60% of peak enzyme activity after inhibition. CUDC-101 treatment increases the acetylation of histone H3 and H4, as well as the acetylation of non-histone substrates of HDAC such as p53 and α-tubulin, in a dose-dependant manner in various cancer cell lines. CUDC-101 also suppresses HER3 expression, Met amplification, and AKT reactivation in tumor cells. [2]
In Vivo Administration of CUDC-101 at 120 mg/kg/day induces tumor regression in the Hep-G2 liver cancer model, which is more efficacious than that of erlotinib at its maximum tolerated dose (25 mg/kg/day) and vorinostat at an equimolar concentration dose (72 mg/kg/day). CUDC-101 inhibits the growth of erlotinib-sensitive H358 NSCLC xenografts in a dose-dependent manner. CUDC-101 also shows potent inhibition of tumor growth in the erlotinib-resistant A549 NSCLC xenograft model. CUDC-101 produces significant tumor regression in the lapatinib-resistant, HER2-negative, EGFR-overexpressing MDA-MB-468 breast cancer model and the EGFR-overexpressing CAL-27 head and neck squamous cell carcinoma (HNSCC) model. Additionally, CUDC-101 inhibits tumor growth in the K-ras mutant HCT116 colorectal and EGFR/HER2 (neu)-expressing HPAC pancreatic cancer models. [1]
Clinical Trials A Phase I study of in subjects with advanced head and neck, gastric, breast, liver and non-small cell lung cancer tumors is ongoing.
Features
Protocol
Kinase Assay [1]
HDAC, EGFR and HER2 inhibition assays The activities of Class I and II HDACs are assessed using the Biomol Color de Lys system. Briefly, HeLa cell nuclear extracts are used as a source of HDACs. Different concentrations of CUDC-101 are added to HeLa cell nuclear extracts in the presence of a colorimetric artificial substrate. Developer is added at the end of the assay and enzyme activity is measured in the Wallac Victor II 1420 microplate reader at 405 nM. EGFR and HER2 kinase activity are measured using HTScan EGF receptor and HER2 kinase assay kits. Briefly, the GST-EGFR fusion protein is incubated with synthetic biotinylated peptide substrate and varying concentrations of CUDC-101 in the presence of 400 mM ATP. Phosphorylated substrate is captured with strapavidin-coated 96-well plates. The level of phosphorylation is monitored by antiphospho-tyrosine- and europium-labeled secondary antibodies. The enhancement solution is added at the end of the assay and enzyme activity is measured in the Wallac Victor II 1420 microplate reader at 615 nM.
Cell Assay [1]
Cell Lines HCC827, H358, H460, HepG2, Hep3B2, Sk-Hep-1, Capan1, BxPc3, MCF-7, MDA-MB-231, and Sk-Br-3
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 72 hours
Methods Cancer cell lines are plated at 5000 to 10000 cells per well in 96-well flatbottomed plates with varying concentrations of CUDC-101. The cells are incubated with CUDC-101 for 72 hours in the presence of 0.5% of fetal bovine serum. Growth inhibition is assessed by an adenosine triphosphate (ATP) content assay using the Perkin-Elmer ATPlite kit. Apoptosis is routinely assessed by measuring the activities of Caspase-3 and -7 using Apo-ONE Homogeneous Assay Kit.
Animal Study [1]
Animal Models Female athymic mice (nude nu/nu CD-1) inoculated with Hep-G2, H358, A549, MDA-MB468, HCT116, CAL-27, HepG2, or HPAC
Formulation Formulated in 30% Captisol solution
Doses ~120 mg/kg/day
Administration Administered via i.v.
References
[1] Cai X, et al. J Med Chem, 2010, 53(5), 2000-2009.
[2] Lai CJ, et al. Cancer Res, 2010, 70(9), 3647-3656.
Toronto Research Chemicals -  C834500 external link
CUDC-101 is a potent multi-acting HDAC (histone deacetylase), EGFR (epidermal growth factor receptor), and HER2 ( human epidermal growth factor receptor 2) inhibitor for the treatment of cancer.

参考文献

参考文献

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