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849217-68-1 分子结构
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1-N'-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

ChemBase编号:72531
分子式:C28H24FN3O5
平均质量:501.5056632
单一同位素质量:501.1699991
SMILES和InChIs

SMILES:
c12c(c(ccn1)Oc1ccc(cc1)NC(=O)C1(C(=O)Nc3ccc(cc3)F)CC1)cc(c(c2)OC)OC
Canonical SMILES:
COc1cc2c(ccnc2cc1OC)Oc1ccc(cc1)NC(=O)C1(CC1)C(=O)Nc1ccc(cc1)F
InChI:
InChI=1S/C28H24FN3O5/c1-35-24-15-21-22(16-25(24)36-2)30-14-11-23(21)37-20-9-7-19(8-10-20)32-27(34)28(12-13-28)26(33)31-18-5-3-17(29)4-6-18/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34)
InChIKey:
ONIQOQHATWINJY-UHFFFAOYSA-N

引用这个纪录

CBID:72531 http://www.chembase.cn/molecule-72531.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
1-N'-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
IUPAC传统名
cabozantinib
别名
BMS-907351
Cabozantinib
XL184
CAS号
849217-68-1
PubChem SID
162037456
PubChem CID
25102847

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 价格
Selleck Chemicals
S1119 external link 加入购物车 请登录
数据来源 数据ID
PubChem 25102847 external link

理论计算性质

理论计算性质

JChem
Acid pKa 13.461886  质子受体
质子供体 LogD (pH = 5.5) 4.162173 
LogD (pH = 7.4) 4.645291  Log P 4.6580625 
摩尔折射率 136.1206 cm3 极化性 52.4303 Å3
极化表面积 98.78 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
DMSO expand 查看数据来源
保存条件
-20°C expand 查看数据来源
作用靶点
c-Kit expand 查看数据来源
c-Met expand 查看数据来源
Flt expand 查看数据来源
Tie-2 expand 查看数据来源
VEGFR expand 查看数据来源
成盐信息
Free Base expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals
Selleck Chemicals -  S1119 external link
Biological Activity
Description XL184 (Cabozantinib) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM.
Targets

VEGFR2

IC50 0.035 nM [1]
In Vitro XL-184 also displays potent activity against c-Met, Ret, Kit, Flt-1, Flt-3, Flt-4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM, 11.3 nM, 6 nM, 14.3 nM and 7 nM, respectively. XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM. [1] XL184 at low concentration (0.1-0.5 μM) is sufficient to induce marked inhibition of constitutive and inducible Met phosphorylation and its resultant downstream signaling in MPNST cells, and inhibit HGF-induced MPNST cell migration and invasion. XL184 also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although XL-184 has no significant effect on MPNST cell growth at 0.1 μM, XL184 at 5-10 μM significantly inhibits the MPNST cell growth. [2]
In Vivo XL184 treatment at 30 mg/kg in RIP-Tag2 mice with spontaneous pancreatic islet tumors disrupts 83% of the tumor vasculature, reduces pericytes and empty basement membrane sleeves, causes widespread intratumoral hypoxia and extensive tumor cell apoptosis, and slows regrowth of the tumor vasculature after drug withdrawal, more significantly compared with XL999 that blocks VEGFR but not c-Met, leading to only 43% reduction in vascularity, suggesting that concurrent inhibition of VEGFR and other functionally relevant receptor tyrosine kinases (RTK) amplifies angiogenesis inhibition. XL184 also decreases invasiveness of primary tumors and reduces metastasis. [1] XL184 at 30 mg/kg/day significantly abrogates human MPNST xenografts growth and metastasis in SCID mice. [2] Administration of XL184 induces dose-dependent inhibition of tumor growth in breast, lung, and glioma tumor models, in association with decreased tumor and endothelial cell proliferation as well as increased apoptosis. A single oral dose of XL184 is sufficient to induce sustained tumor growth inhibition in MDA-MB-231 tumor-bearing mice and C6 tumor-bearing rats at 100 mg/kg and 10 mg/kg, respectively. [3]
Clinical Trials XL184 is currently under Phase III study versus mitoxantrone plus prednisone in men with previously treated symptomatic castration-resistant prostate cancer (COMET-2).
Features
Protocol
Cell Assay [2]
Cell Lines ST88-14, STS26T, and MPNST724
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 48 hours
Methods

Cells are exposed to various concentrations of XL184 for 48 hours. Cell growth is determined by MTS assays using CellTiter96 Aqueous Non-Radioactive Cell Proliferation Assay kit. Absorbance is measured at a wavelength of 490 nm, and the absorbance values of treated cells are presented as a percentage of the absorbance of untreated cells.

Animal Study [1]
Animal Models RIP-Tag2 transgenic mice in a C57BL/6 background with spontaneous pancreatic islet tumors
Formulation Suspended at a concentration of 5 mg/mL in sterile saline or water
Doses ~60 mg/kg
Administration Oral gavage
References
[1] You WK, et al. Cancer Res, 2011, 71(14), 4758-4768.
[2] Torres KE, et al. Clin Cancer Res, 2011, 17(12), 3943-3955.
[3] Yakes FM, et al. Mol Cancer Ther, 2011, 10(12), 2298-2308.

参考文献

参考文献

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专利

专利

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