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379231-04-6 分子结构
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N-(5-chloro-2H-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine

ChemBase编号:72455
分子式:C27H32ClN5O5
平均质量:542.02648
单一同位素质量:541.20919683
SMILES和InChIs

SMILES:
c1c(cc2c(c1OC1CCOCC1)c(ncn2)Nc1c(ccc2c1OCO2)Cl)OCCN1CCN(CC1)C
Canonical SMILES:
CN1CCN(CC1)CCOc1cc(OC2CCOCC2)c2c(c1)ncnc2Nc1c(Cl)ccc2c1OCO2
InChI:
InChI=1S/C27H32ClN5O5/c1-32-6-8-33(9-7-32)10-13-35-19-14-21-24(23(15-19)38-18-4-11-34-12-5-18)27(30-16-29-21)31-25-20(28)2-3-22-26(25)37-17-36-22/h2-3,14-16,18H,4-13,17H2,1H3,(H,29,30,31)
InChIKey:
OUKYUETWWIPKQR-UHFFFAOYSA-N

引用这个纪录

CBID:72455 http://www.chembase.cn/molecule-72455.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
N-(5-chloro-2H-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine
IUPAC传统名
N-(5-chloro-2H-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine
别名
Saracatinib
AZD0530(Saracatinib)
N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methyl-1-piperazinyl)ethoxy]-5-[(tetrahydro-2H-pyran-4-yl)oxy]-4-quinazolinamine
7-[2-[4-Methylpiperazin-1-yl]ethoxy]-5-[[tetrahydropyran-4-yl]oxy]-4-[[6-chloro-2,3-methylenedioxyphenyl]amino]quinazoline
Saracatinib
CAS号
379231-04-6
PubChem SID
162037380
PubChem CID
10302451

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 10302451 external link

理论计算性质

理论计算性质

JChem
Acid pKa 11.810066  质子受体 10 
质子供体 LogD (pH = 5.5) 0.48819196 
LogD (pH = 7.4) 2.3390348  Log P 3.1983316 
摩尔折射率 143.643 cm3 极化性 56.868195 Å3
极化表面积 90.44 Å2 可自由旋转的化学键
里宾斯基五规则 false 

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
Chloroform expand 查看数据来源
DMSO expand 查看数据来源
Methanol expand 查看数据来源
外观
White Solid expand 查看数据来源
熔点
84-89°C expand 查看数据来源
保存条件
-20°C expand 查看数据来源
-20°C Freezer 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
Bcr-Abl expand 查看数据来源
SRC 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 -  S1006 external link
Research Area
Description Cancer
Biological Activity
Description Saracatinib (AZD0530) is a Src inhibitor for c-Src with IC50 of 2.7 nM.
Targets c-Src
IC50 2.7 nM [1]
In Vitro Saracatinib also potently inhibits other Src tyrosine kinase family members including c-Yes, Fyn, Lyn, Blk, Fgr, and Lck with IC50 from 4-10 nM. Saracatinib sensitively inhibits Src Y530F NIH 3T3 with IC50 of 80 nM. Saracatinib significantly impairs the invasion of HT1080 cells through a 3-dimensional collagen matrix and completely inhibits EGF-induced cell scattering in NBT-II bladder cancer cells. [1] Saracatinib potent inhibits Src activation in DU145 and PC3 cells, which through inhibition of Y419 phosphorylation. Saracatinib inhibits the growth of prostate cancer including PC3, DU145, CWR22Rv1 and LNCaP, while Saracatinib shows low activity in LAPC-4, PZ-HPV7 and RWPE-1 cells. Saracatinib induces cell cycle arrest at G1/S but not caspase 3 cleavages. Saracatinib also significantly inhibits DU145 and PC3 migration in the Boyden chamber. [2] Saracatinib gives a potent and sustained blockage of AKT and enhancs the sensitivity to irradiation in A549 and Calu-6 cells. [3] Saracatinib inhibits osteoclast in activity, resorption and formation. Saracatinib also reversibly prevents osteoclast precursor migration. [4]
In Vivo Saracatinib shows great tumor growth inhibiton in Src3T3 allografts and a moderate growth delay in Calu-6, MDA-MB-231, AsPc-1 and BT474C xenografts. [1] Saracatinib shows great antitumor activity in orthotopic DU145 xenograft mice at a dose of 25mg/kg (orally administered, daily). [2]
Clinical Trials Saracatinib is currently in Phase II clinical trial in recurrent osteosarcoma localized to the lung.
Features Saracatinib is the first Src inhibitor to show inhibition of the Src pathway in human tumor tissue.
Combination Therapy
Description AZD0530 at concentration of 1 μM combined with Imatinib at concentration of 0.1 μM show an additive inhibitory effect on the proliferation of CML BV173 cells. [5] AZD0530 at concentration of 1 μM in combination with Tamoxifen at concentration ranging from 1 nM to 10 μM show improved growth inhibitory effects in both MCF7 and T47D cells, with decreased Ki67 expression. AZD0530 combined with Tamoxifen result in a reduction of Src activity together with inhibition of focal adhesion kinase phosphorylation and a complete abrogation of their in vitro invasive behaviour in both MCF7 and T47D cells. [6] AZD0530 at concentration of 1 μM in combination with Anastrozole at concentration of 100 μM increase p27 and cause greater G(1) cell cycle arrest in MCF-7Arom5 cells. AZD0530 administrated at dose of 50 mg/kg by oral gavage in combination with Anastrozole subcutaneously injected at dose of 0.25 mg/kg or 5 μg/animal reduce drug resistance and show greater antitumor efficacy with greater Src and EGFR inhibition and a greater increase in p27 and reduction of Ki-67 in MCF-7Arom5 tumor xenografts mice. [7]
Protocol
Kinase Assay [1]
Kinase Assay IC50 of tyrosine kinase activity is measured by an enzyme-linked immunosorbent assay (ELISA) with recombinant catalytic domains of a panel of receptor and non-receptor tyrosine kinases (in some cases only part of the catalytic domain is used). Saracatinib dose ranges from 0.001–10 mM. Speci?city assays against a panel of serine/threonine kinases are performed using a ?lter capture assay with 32P. Briefly, multidrop 384 plates containing 0.5 μL Saracatinib or controls (DMSO) alone or pH 3.0 buffer controls) are incubated with 15 μL of enzyme plus peptide/protein substrate for 5 min before the reaction is initiated by the addition of 10 μL of 20 mM Mg-ATP. For all enzymes the ?nal concentration is approximated to the Michaelis constant (Km). Assays are carried out for 30min at room temperature before termination by the addition of 5 μL orthophosphoric acid. After mixing, the well contents are harvested onto a P81 Uni?lter plate, using orthophosphoric acid as the wash buffer. Then IC50 is calculated.
Cell Assay [1]
Cell Lines PC3, DU145, CWR22Rv1, LNCaP, LAPC-4, PZ-HPV7 and RWPE-1 cells
Concentrations 62.5 nM - 16 mM
Incubation Time 1, 3 and 5 days
Methods Cells are seeded at a density of 2×103 in 96-well plates and incubated overnight. Then Saracatinib (62.5 nM–16 mM) is added to the cells. After 1, 3 and 5 days, culture medium is removed followed by addition of 0.2 mL DMSO per well and continuous shaking of plates at 200 rotations per minute for 15min. Then IC50 is measured by MTT method.
Animal Study [1]
Animal Models CB17 mice are implanted with DU145 cells.
Formulation Dissolved in 0.5% hydroxypropyl methylcellulose, 0.1% Tween 80
Doses 25 mg/kg
Administration Orally administered daily
References
[1] Chang YM, Oncogene, 2008, 27(49), 6365-6375.
[2] Green TP, et al. Mol Oncol, 2009, 3(3), 248-261.
[3] Purnell PR, et al. J Thorac Oncol, 2009, 4(4), 448-454.
[4] de Vries TJ, et al. Mol Cancer Res, 2009, 7(4), 476-488.
[5] Gwanmesia PM, et al. BMC Cancer, 2009, 13;9:53.
[6] Hiscox S, et al. Breast Cancer Res Treat, 2009, 115(1), 57-67.
[7] Chen Y, et al. Clin Cancer Res, 2009, 15(10), 3396-3405.
Toronto Research Chemicals -  S139350 external link
An oral, selective dual inhibitor of Src and ABL kinase.

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