ON 146040

ON 146040 was highly potent in killing hematologic tumor cells with IC50 values in the 150 to 1,000 nM range. In biochemical testing, ON 146040 inhibited PI3K / isoforms (IC50  14 and 20 nM, respectively) without having a major effect on / isoforms (IC50  3 and 1 M, respectively). ON 146040 was also found to inhibit Abl1 and several mutant versions of this kinase (IC50 < 150 nM), although the compound was not found to be active against the T315I mutant. Following treatment with ON 146040, STAT3 and STAT5 phosphorylation were down-regulated in leukemia and myeloma cells.