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1116235-97-2 分子结构
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2-{[2-({1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydro-1H-indol-6-yl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-6-fluoro-N-methylbenzamide

ChemBase编号:73188
分子式:C27H29FN8O3
平均质量:532.5693632
单一同位素质量:532.23466505
SMILES和InChIs

SMILES:
n1c(nc2c(c1Nc1cccc(c1C(=O)NC)F)cc[nH]2)Nc1c(cc2c(c1)N(CC2)C(=O)CN(C)C)OC
Canonical SMILES:
CNC(=O)c1c(cccc1F)Nc1nc(Nc2cc3c(cc2OC)CCN3C(=O)CN(C)C)nc2c1cc[nH]2
InChI:
InChI=1S/C27H29FN8O3/c1-29-26(38)23-17(28)6-5-7-18(23)31-25-16-8-10-30-24(16)33-27(34-25)32-19-13-20-15(12-21(19)39-4)9-11-36(20)22(37)14-35(2)3/h5-8,10,12-13H,9,11,14H2,1-4H3,(H,29,38)(H3,30,31,32,33,34)
InChIKey:
HZTYDQRUAWIZRE-UHFFFAOYSA-N

引用这个纪录

CBID:73188 http://www.chembase.cn/molecule-73188.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
2-{[2-({1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydro-1H-indol-6-yl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-6-fluoro-N-methylbenzamide
IUPAC传统名
2-{[2-({1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-6-fluoro-N-methylbenzamide
别名
GSK1838705A
CAS号
1116235-97-2
PubChem SID
162038108
PubChem CID
25182616

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
S2703 external link 加入购物车 请登录
数据来源 数据ID
PubChem 25182616 external link

理论计算性质

理论计算性质

JChem
Acid pKa 11.803308  质子受体
质子供体 LogD (pH = 5.5) 1.8360311 
LogD (pH = 7.4) 3.8439407  Log P 4.061565 
摩尔折射率 146.3655 cm3 极化性 54.47305 Å3
极化表面积 127.51 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

安全信息 药理学性质 产品相关信息 生物活性(PubChem)
保存条件
-20°C expand 查看数据来源
作用靶点
IGF-1 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 -  S2703 external link
Research Area
Description Cancer
Biological Activity
Description GSK1838705A is a potent inhibitor of IGF-IR, IR and ALK with IC50 of 2.0 nM, 1.6 nM and 0.5 nM, respectively
Targets IGF-IR IR ALK
IC50 2 nM 1.6 nM 0.5 nM [1]
In Vitro GSK1838705A potently and ATP-competitively inhibits IGF-IR and IR with appKi values of 0.7 nM and 1.1 nM, respectively.In cells, GSK1838705A potently inhibits ligand-induced phosphorylation of IGF-IR and IR with IC50 of 85 nM and 79 nM, respectively. GSK1838705A shows the significant anti-proliferative effect in a panel of cell lines derived from solid and hematologic tumors such as L-82, SUP-M2, SK-ES and MCF-7 cells with EC50 of 24 nM, 28 nM, 141 nM and 203 nM, respectively. GSK1838705A shows an accumulation of MCF-7 and NCl-H929 cells predominantly in G1 (2N) phase of the cell cycle. GSK1838705A also inhibits ALK with Ki of 0.35 nM and supresses the proliferation of nucleophosmin (NPM)-ALK fusion cells with EC50 of 24-88 nM. GSK1838705A potently inhibits NPM-ALK phosphorylation in Karpas-299 and SR-786 cells, while has modest effect on STAT3 phosphorylation. [1]
In Vivo In NIH-3T3/LISN tumor-bearing mice, oral treatment of GSK1838705A (60 mg/kg) cause tumor growth inhibition by 77%, without significant weight loss. In COLO 205 tumor–bearing mice, inhibition of tumor growth by GSK1838705A (30 mg/kg) is 80%. Besides, the antitumor efficacy of GSK1838705A is also observed in mice bearing HT29 xenograft or BxPC3 xenograft. In mice, GSK1838705A (60 mg/kg) leads to a transient 2-fold increase in blood glucose levels by inhibiting IR signaling. GSK1838705A (60 mg/kg) inhibits the growth of established Karpas-299 xenografts with 93% tumor growth inhibition, with no effect on weights of the rats. [1]
Clinical Trials
Features GSK1838705A is a small-molecule kinase inhibitor of IGF-IR and the insulin receptor.
Protocol
Kinase Assay [1]
Kinase Assays Baculovirus-expressed glutathione S-transferase–tagged proteins encoding the intracellular domain of IGF-IR (amino acids 957–1367) and IR (amino acids 979–1382) are used for determinations of IC50s by a homogeneous time-resolved fluorescence assay. A filter binding assay is used for appKi determinations using activated IGF-IR and IR kinases. Expanded kinase-selectivity profiling of GSK1838705A is carried out by screening the compound in the KinaseProfiler panel.
Cell Assay [1]
Cell Lines L-82, SUP-M2, SK-ES and MCF-7
Concentrations 0 to 10 μM
Incubation Time 72 hours
Methods Cells are seeded in 96-well dishes, incubated overnight at 37 °C, and treated with DMSO or GSK1838705A for 72 hours. For the NIH-3T3/LISN proliferation assays, cells are seeded on collagen-coated 96-well tissue culture plates and allowed to adhere for 24 hours. The medium is replaced with serum-free medium and the cells are treated with GSK1838705A for 2 hour. Cells are incubated for 72 hours after addition of IGF-I (30 ng/mL). Cell proliferation is quantified using the CellTiter-Glo Luminescent Cell Viability Assay. IC50s are determined from cytotoxicity curves using a four-parameter curve fit software package (XLfit4).
Animal Study [1]
Animal Models L-82, SUP-M2, SK-ES and MCF-7 cells are injected s.c. into the right flank of CD1 or SCID mice.
Formulation GSK1838705A is dissolved in 20% sulfobutyl ether β-cyclodextrin (ISP; pH 3.5).
Doses ≤60 mg/kg
Administration Administered via p.o.
References
[1] Sabbatini P, et al. Mol Cancer Ther. 2009, 8(10), 2811-2820.

参考文献

参考文献

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