SGI-1776 free base is an ATP competitive inhibitor of Pim1 with IC50 of 7 nM in a cell-free assay, 50- and 10-fold selective versus Pim2 and Pim3, also potent toFlt3 and haspin.
Pim (provirus integration site for Moloney murine leukemia virus) family proteins are highly conserved serine/threonine kinases implicated in transcription, translation, cell cycle, survival, and drug resistance through the numerous targets. SGI-1776 is a dual Pim/FLT3 with IC50 values of 7nM, 363nM, 69nM and 44nM for Pim-1, Pim-2, Pim-3 (measurd by Kinase assays) and FLT3, respectively. Treatment with SGI-1776 at concentration<10μM caused decreased of p-H3-S10, p-cMyc-S62, p-BAD-S112, p-4E-BP1-Thr37/46, Mcl-1, as well as increased p27 in AML cell line MV-4-11. However, the decreased p-Bad-S112 and p-H3-S10 by SGI-1776 treatment were not observed in CLL lines, suggesting an alternative mechanism in different type of cells[1][2]. Incubation with 1, 3, and 10μM SGI-1776 for 24h resulted in an average increase in apoptosis of 10%, 22%, and 38% in CLL lymphocytes, mechanism of which may involved Mcl-1 reduction[1]. Also dose-dependent induction of cell death and reduction of clonogenic survival by SGI-1776<10μM can be observed in AML cell lines. Oral treatment with SGI-1776 at dose of 75mg/kg, QD, 5 days per week, for 3 weeks or 200mg/kg twice a week for 3 weeks could significantly reduce tumor growth in mice bearing MV-4-11 tumors[2].
SGI-1776 free base 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
CHO cells
Function assay
Inhibition of human ERG expressed in CHO cells by automated patch clamp method, IC50=1 μM
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