GSK1838705A 是一种高效的、可逆的IGF-IR (IC50:2.0 nM) 和胰岛素受体 (IC50:1.6 nM)抑制剂，也可抑制ALK (IC50:0.5 nM)。

GSK1838705A is an effective IGF-1R inhibitor (IC50: 2.0 nM), modestly potent to IR (IC50: 1.6 nM) and ALK (IC50: 0.5 nM), respectively, and little inhibition to other protein kinases.

在负荷COLO 205肿瘤的小鼠体内,GSK1838705A（30 mg/kg）可抑制80%的肿瘤生长.此外,在负荷HT29异种移植物或BxPC3异种移植物的小鼠体内,GSK1838705A也具有抗肿瘤作用.在负荷NIH-3T3/LISN肿瘤的小鼠体内,GSK1838705A（60 mg/kg,p.o.）抑制77%肿瘤生长,且体重无明显损失.在小鼠体内,通过抑制IR信号,GSK1838705A（60 mg/kg）可使血糖水平短暂增加2倍.GSK1838705A（60 mg/kg）抑制已建立的Karpas-299异种移植物的生长（93%）,但不影响大鼠体重.

GSK1838705A可有效抑制细胞中配体诱导的IGF-1R（IC50：85 nM）和IR（IC50：79 nM）磷酸化。GSK1838705A对一系列衍生自固体和血液肿瘤的细胞系,比如L-82/SUP-M2/SK-ES/MCF-7（EC50：24/28/141/203 nM）细胞均有显著抗增殖作用。GSK1838705A可使MCF-7 和NCl-H929细胞在细胞周期的G1 (2N)期积累。GSK1838705A对ALK也有抑制效果（Ki：0.35 nM）,还抑制核仁磷酸蛋白(NPM)-ALK融合细胞的增殖（EC50：24-88 nM）。GSK1838705A对Karpas-299和SR-786细胞中的NPM-ALK磷酸化有显著抑制作用,但对STAT3磷酸化效果一般。

Kinase Assays: Baculovirus-expressed glutathione S-transferase-tagged proteins encoding the intracellular domain of IGF-1R (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-1R and IR kinases. Expanded kinase-selectivity profiling of GSK1838705A is carried out by screening the compound in the KinaseProfiler panel.

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(Only for Reference)

1116235-97-2

C27H29FN8O3

532.58

DMSO:53.3 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years