GSK1838705A
中文名称 | GSK1838705A |
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中文同义词 | 2-[[2-[[1-[(二甲基氨基)乙酰基]-5-(甲氧基)-2,3-二氢-1H-吲哚-6-基]氨基]-7H-吡咯并[2,3-D]嘧啶-4-基]氨基]-6-氟-N-甲基苯甲酰胺;IGF-IR/INSR和ALK抑制剂(GSK1838705A);化合物GSK1838705A |
英文名称 | GSK1838705A |
英文同义词 | GSK1838705A;2-[[2-[[1-[(Dimethylamino)ethanoyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide;2-(2-(1-(2-(dimethylamino)acetyl)-5-methoxyindolin-6-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-6-fluoro-N-methylbenzamide;2-[[2-[[1-[(Dimethylamino)ethanoyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide GSK1838705A;2-[[2-[[1-[2-(Dimethylamino)acetyl]-2,3-dihydro-5-methoxy-1H-indol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methy;2-[[2-[[1-[2-(Dimethylamino)acetyl]-2,3-dihydro-5-methoxy-1H-indol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide;CS-236;Benzamide, 2-[[2-[[1-[2-(dimethylamino)acetyl]-2,3-dihydro-5-methoxy-1H-indol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methyl- |
CAS号 | 1116235-97-2 |
分子式 | C27H29FN8O3 |
分子量 | 532.57 |
EINECS号 | |
相关类别 | 医药中间体;蛋白酪氨酸激酶;小分子抑制剂,天然产物;小分子抑制剂;细胞生物学试剂;Inhibitors |
Mol文件 | 1116235-97-2.mol |
结构式 |
GSK1838705A 性质
密度 | 1.399 |
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储存条件 | -20°C |
溶解度 | 在DMSO中的溶解度为20mg/mL,澄清 |
形态 | 粉末 |
酸度系数(pKa) | 13.27±0.50(Predicted) |
颜色 | 白色至浅棕色 |
GSK1838705A是一种有效的IGF-1R抑制剂,IC50为2.0 nM,适度有效作用于IR和ALK,IC50分别为1.6 nM和0.5 nM,对其他蛋白激酶几乎没有作用活性。GSK1838705A potently and ATP-competitively inhibits IGF-1R and IR with appKi values of 0.7 nM and 1.1 nM, respectively.In cells, GSK1838705A potently inhibits ligand-induced phosphorylation of IGF-1R 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.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.GSK1838705A is a small-molecule kinase inhibitor of IGF-1R and the insulin receptor.GSK1838705A是一种有效的IGF-1R抑制剂,IC50为2.0 nM,适度有效作用于IR和ALK,IC50分别为1.6 nM和0.5 nM,对其他蛋白激酶几乎没有作用活性。
Target | Value |
ALK
(Cell-free assay) | 0.5 nM |
Insulin Receptor
(Cell-free assay) | 1.6 nM |
IGF-1R
(Cell-free assay) | 2 nM |
GSK1838705A有效且ATP竞争性抑制IGF-1R和IR,
在负荷NIH-3T3/LISN肿瘤的小鼠体内,GSK1838705A (60 mg/kg)口服治疗抑制77%肿瘤生长,而没有显著的体重损失。在负荷COLO 205肿瘤的小鼠体内,GSK1838705A (30 mg/kg)能够抑制80%的肿瘤生长。此外,GSK1838705A的抗肿瘤作用在负荷HT29异种移植物或BxPC3异种移植物的小鼠体内也能观察到。在小鼠体内,GSK1838705A (60 mg/kg)通过抑制IR信号,引起血糖水平短暂增加2倍。GSK1838705A (60 mg/kg)抑制已建立的Karpas-299异种移植物的生长,抑制率为93%,而对大鼠的体重没有影响。安全信息
WGK Germany | 3 |
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更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
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2024/08/19 | HY-13020 | GSK1838705A | 1 mg | 351元 | |
2024/08/19 | HY-13020 | GSK1838705A GSK1838705A | 1116235-97-2 | 5mg | 900元 |