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1123889-87-1 分子结构
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N-[4-({3-[(3,5-dimethoxyphenyl)amino]quinoxalin-2-yl}sulfamoyl)phenyl]-3-methoxy-4-methylbenzamide

ChemBase编号:72724
分子式:C31H29N5O6S
平均质量:599.65686
单一同位素质量:599.18385467
SMILES和InChIs

SMILES:
c12ccccc1nc(c(n2)Nc1cc(cc(c1)OC)OC)NS(=O)(=O)c1ccc(cc1)NC(=O)c1ccc(c(c1)OC)C
Canonical SMILES:
COc1cc(OC)cc(c1)Nc1nc2ccccc2nc1NS(=O)(=O)c1ccc(cc1)NC(=O)c1ccc(c(c1)OC)C
InChI:
InChI=1S/C31H29N5O6S/c1-19-9-10-20(15-28(19)42-4)31(37)33-21-11-13-25(14-12-21)43(38,39)36-30-29(34-26-7-5-6-8-27(26)35-30)32-22-16-23(40-2)18-24(17-22)41-3/h5-18H,1-4H3,(H,32,34)(H,33,37)(H,35,36)
InChIKey:
HJSSPYJVWLTYHG-UHFFFAOYSA-N

引用这个纪录

CBID:72724 http://www.chembase.cn/molecule-72724.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-[4-({3-[(3,5-dimethoxyphenyl)amino]quinoxalin-2-yl}sulfamoyl)phenyl]-3-methoxy-4-methylbenzamide
IUPAC传统名
N-[4-({3-[(3,5-dimethoxyphenyl)amino]quinoxalin-2-yl}sulfamoyl)phenyl]-3-methoxy-4-methylbenzamide
别名
XL-765
SAR245409
XL765
CAS号
1123889-87-1
PubChem SID
162037645
PubChem CID
49867926

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
S1523 external link 加入购物车 请登录
数据来源 数据ID
PubChem 49867926 external link

理论计算性质

理论计算性质

JChem
Acid pKa 6.1090965  质子受体
质子供体 LogD (pH = 5.5) 5.464378 
LogD (pH = 7.4) 4.7442193  Log P 5.547877 
摩尔折射率 163.3601 cm3 极化性 63.571304 Å3
极化表面积 140.77 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
mTOR expand 查看数据来源
PI3K 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 -  S1523 external link
Biological Activity
Description XL765 is a dual inhibitor of mTOR/PI3k for mTOR, p110α, p110β, p110γ and p110δ with IC50 of 157 nM, 39 nM, 113 nM, 9 nM and 43 nM, respectively.
Targets mTOR p110α p110β p110γ p110δ
IC50 157 nM 39 nM 113 nM 9 nM 43 nM [1]
In Vitro XL765 is active against class I PI3K (IC50 = 39, 113, 9 and 43 nM for p110α, β, γ and δ, respectively). XL765 also inhibits DNA-PK (IC50 = 150 nM) and mTOR (IC50 = 157 nM) but not XL-147 which shows IC50 values of > 15 μM. [1] XL765 treatment results in decreased cell viability in 13 PDA cell lines in a dose-dependent manner. XL765, a dual-target PI3K/mTOR inhibitor, inhibits cell growth and apoptosis in many more cell lines and at lower concentrations as compared to the PI3K-selective inhibitors XL147 and PIK90. The effect can be recapitulated by using combinations of single-targeted compounds. XL765 significantly reduces phosphorylation of the mTOR targets S6, S6K, and 4EBP1, which is associated with greater apoptosis induction rather than to PI3K inhibition alone. XL765 treatment causes accumulation of autophagosomes in MIAPaCa-2 cells, and results in significant dose-dependent AVO induction and LC3-II stimulation in MIAPaCa-2 cells stably expressing a LC3-GFP construct. [2]
In Vivo The combination of XL765 (30 mg/kg) with chloroquine (50 mg/kg) results in significant inhibition of BxPC-3 xenograft growth in mice models, while XL765 alone at the same dose has no inhibitory effect. [2] Oral administration of XL765 results in greater than 12-fold reduction in median tumor bioluminescence compared to control and improvement in median survival in nude mice implanted intracranially with GBM 39-luc cells. XL765 in combination with temozolomide (TMZ) yields a 140-fold reduction in median bioluminescence with a trend toward improvement in median survival compared with TMZ alone. [3]
Clinical Trials A Phase I study to evaluate the safety and tolerability of XL765 in combination with erlotinib in subjects with solid tumors has been completed.
Features
Protocol
Kinase Assay [1]
Cell Assay [2]
Cell Lines Pancreatic cancer cell lines (HcG25, Panc89, PA-TU8988T, Panc2.13, MiaPaCa2, Panc10.05, Panc8.13, BxPC-3, etc.)
Concentrations Dissolved in DMSO, final concentration ~10 μM
Incubation Time 24, 48, 72 hours
Methods Cells are treated with XL765 24 hours after plating and harvested for apoptosis or autophagy assays at 24, 48, or 72 hours after XL765 treatment. Apoptosis is determined by total percentage of annexin V-positive cells by fluorescence-activated cell sorting (FACS). Acidic vesicular organelles (AVOs) are detected in XL765-treated cells by vital staining with acridine orange. The degree of AVO formation is expressed as fold increase of acridine orange fluorescence intensity (FL3) in XL765-treated cells versus control cells.
Animal Study [2]
Animal Models Female Nu/Nu mice inoculated s.c. with BxPC-3 cells
Formulation Solubilized in water/10 mM HCl
Doses 30 mg/kg
Administration Oral gavage once a day
References
[1] Garcia-Echeverria C, et al. Oncogene, 2008, 27(41), 5511-5526.
[2] Mirzoeva OK, et al. J Mol Med, 2011, 89(9), 877-889.
[3] Prasad G, et al. Neuro Oncol, 2011, 13(4), 384-392.

参考文献

参考文献

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专利

专利

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