GSK1904529A is a selective inhibitor of IGF-1R and IR with IC50 of 27 nM and 25 nM, being > 100-fold selective for IGF-1R/InsR than Akt1/2, Aurora A/B,B-Raf, CDK2, EGFR etc.
IGF-1R (insulin-like growth factor-1 receptor) plays a key role in transformation, growth and survival of malignant cells, and has been considered as a general and promising target for cancer treatment. GSK1904529A is a selective inhibitor of IGF-IR and IR with IC50 values of 27 and 25nM, respectively. Treatment with GSK1904529A ranging in 0.03-3μM dose-dependently inhibited IGF-1- or insulin-induced autophosphorylation of IGF-1R, as well as the downstream signaling, including phosphorylation of ATK, IRS-1 and ERK. And this inhibition on phosphorylation on IGF-1R and its downstream can be also observed in vivo. In COLO 205, MCF-7, and NCI-H929 cells treated with GSK1904529A ranging in 0.3-10μM for 24h or 48h, dose-dependent increased accumulation in G1 of the cell cycle could be observed. GSK1904529A showed anti-proliferation of cell lines derived from solid and hematologic malignancies, among which multiple myeloma and Ewing’s sarcoma cell lines showed most sensitivity. Oral administration of GSK1904529A at 30mg/kg once daily or twice daily for 21 days significantly inhibited tumor growth inhibition of female nude mice bearing tumor xenografts of NIH-3T3/LISN, COLO 205, HT29 and BxPC3, respectively. As GSK1904529A is also a IR inhibitor, minimal effects on blood glucose levels can be observed in animals treated with a single dose of 30 mg/kg GSK1904529A[1].
作用机制
GSK1904529A is a reversible, ATP-competitive inhibitor.[1]
GSK1904529A 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
human COLO205 cells
Proliferation assay
72 h
Antiproliferative activity against human COLO205 cells after 72 hrs by Celltiter assay, IC50=124 nM
19101143
human LP-1 cells
Proliferation assay
72 h
Antiproliferative activity against human LP-1 cells after 72 hrs by Celltiter assay, IC50=104 nM
19101143
human NCI-H929 cells
Proliferation assay
72 h
Antiproliferative activity against human NCI-H929 cells after 72 hrs by Celltiter assay, IC50=81 nM
19101143
human SK-ES cells
Proliferation assay
72 h
Antiproliferative activity against human SK-ES cells after 72 hrs by Celltiter assay, IC50=61 nM
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