ON 146040 is a potent, dual PI3K/BCR-ABL inhibitor with IC50 of 14/20 nM for PI3Kα/δ , IC50 of 20 nM for BCR/ABL.
ON 146040 displays no significant effect on PI3Kβ/γ isoforms (IC50=3/1 uM), also inhibits Abl1 and several mutant versions of Abl (IC50<150 nM) but not the T315I mutant.
ON 146040 abrogates the oncogenic signaling of STAT3 and STAT5.
ON 146040 is highly potent in killing hematologic tumor cells with IC50 values of 150-1,000 nM, down-regulates STAT3 and STAT5 phosphorylation in leukemia and myeloma cells.
