1116235-97-2
中文名稱
GSK1838705A
英文名稱
GSK1838705A
CAS
1116235-97-2
分子式
C27H29FN8O3
分子量
532.57
MOL 文件
1116235-97-2.mol
更新日期
2024/12/23 09:09:17
1116235-97-2 結(jié)構(gòu)式
基本信息
中文別名
化合物GSK1838705AIGF-IR/INSR和ALK抑制劑(GSK1838705A)
2-[[2-[[1-[(二甲基氨基)乙?；鵠-5-(甲氧基)-2,3-二氫-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
英文別名
CS-236GSK1838705
GSK1838705A
GSK1838705A USP/EP/BP
GSK1838705A >=98% (HPLC)
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-[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
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-
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
所屬類別
生物化工：蛋白酪氨酸激酶物理化學(xué)性質(zhì)
密度1.399
儲存條件?20°C
儲存條件-20°C
溶解度在DMSO中的溶解度為20mg/mL，澄清
酸度系數(shù)(pKa)13.27±0.50(Predicted)
形態(tài)粉末
顏色白色至淺棕色
常見問題列表
生物活性
GSK1838705A是一種有效的IGF-1R抑制劑，IC50為2.0 nM，適度有效作用于IR和ALK，IC50分別為1.6 nM和0.5 nM，對其他蛋白激酶幾乎沒有作用活性。體外研究
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.體內(nèi)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.靶點(diǎn)
| Target | Value |
|
ALK
(Cell-free assay) | 0.5 nM |
|
Insulin Receptor
(Cell-free assay) | 1.6 nM |
|
IGF-1R
(Cell-free assay) | 2 nM |
體外研究
GSK1838705A有效且ATP競爭性抑制IGF-1R和IR，
體內(nèi)研究
在負(fù)荷NIH-3T3/LISN腫瘤的小鼠體內(nèi)，GSK1838705A (60 mg/kg)口服治療抑制77%腫瘤生長，而沒有顯著的體重?fù)p失。在負(fù)荷COLO 205腫瘤的小鼠體內(nèi)，GSK1838705A (30 mg/kg)能夠抑制80%的腫瘤生長。此外，GSK1838705A的抗腫瘤作用在負(fù)荷HT29異種移植物或BxPC3異種移植物的小鼠體內(nèi)也能觀察到。在小鼠體內(nèi)，GSK1838705A (60 mg/kg)通過抑制IR信號，引起血糖水平短暫增加2倍。GSK1838705A (60 mg/kg)抑制已建立的Karpas-299異種移植物的生長，抑制率為93%，而對大鼠的體重沒有影響。