GSK1838705A

生物活性体外研究体内研究特征生物活性靶点体外研究体内研究 GSK1838705A 试剂级价格

GSK1838705A

CAS号:1116235-97-2
英文名:GSK1838705A
中文名:GSK1838705A
CBNumber:CB72605356
分子式:C27H29FN8O3
分子量:532.57
MOL File:1116235-97-2.mol

GSK1838705A化学性质

密度 :1.399
储存条件 :-20°C
溶解度 :DMSO: soluble20mg/mL, clear
形态 :powder
酸度系数(pKa) :13.27±0.50(Predicted)
颜色 :white to light brown

安全信息

WGK Germany :3

GSK1838705A性质、用途与生产工艺

生物活性 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。
体外研究 GSK1838705A potently and ATP-competitively inhibits IGF-1R and IR with ^appK_i 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 K_i 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.
体内研究 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.
特征 GSK1838705A is a small-molecule kinase inhibitor of IGF-1R and the insulin receptor.
生物活性 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。
靶点
Target Value
ALK
(Cell-free assay) 0.5 nM
Insulin Receptor
(Cell-free assay) 1.6 nM
IGF-1R
(Cell-free assay) 2 nM
体外研究
GSK1838705A有效且ATP竞争性抑制IGF-1R和IR，
体内研究在负荷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。