1404231-34-0
1404231-34-0 结构式
基本信息
化合物ON 146040
(7Z)-2-[4-(4-methylpiperazin-1-yl)anilino]-7-[(4-nitrophenyl)methylidene]-5H-pyrimido[4,5-b][1,4]thiazin-6-one
5H-Pyrimido[4,5-b][1,4]thiazin-6(7H)-one, 2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-7-[(4-nitrophenyl)methylene]-
常见问题列表
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PI3Kα 14 nM (IC 50 ) |
PI3Kδ 20 nM (IC 50 ) |
PI3Kγ 1 μM (IC 50 ) |
PI3Kβ 3 μM (IC 50 ) |
In biochemical testing, ON 146040 inhibits PI3Kα/ PI3Kδ isoforms (IC 50 ≈14 and 20 nM, respectively) without having a major effect on PI3Kβ/ PI3Kγ isoforms (IC 50 ≈3 and 1 μM, respectively). ON 146040 is also found to inhibit Abl1 and several mutant versions of this kinase (IC 50 <150 nM), although ON 146040 is not found to be active against the T315I mutant. ON 146040 represents the first dual PI3K and BCR-ABL inhibitor that targets the STAT3 and STAT5 pathways. ON 146040 disrupts the oncogenic activity of both STAT3 and STAT5 by targeting upstream activators, including PI3K α and δ isoforms as well as wild type and mutant BCR-ABL. ON 146040 is highly potent in killing hematologic tumor cells with IC 50 values in the 150 to 1,000 nM range. Following treatment with ON 146040, STAT3 and STAT5 phosphorylation are down-regulated in leukemia and myeloma cells.