PD180970 is a novel Bcr-Abl inhbiitor. PD180970 inhibited in vivo tyrosine phosphorylation of p210Bcr-Abl (IC50 = 170 nM) and the p210BcrAbl substrates Gab2 and CrkL (IC50 = 80 nM) in human K562 chronic myelogenous leukemic cells. In vitro, PD180970 potently inhibited autophosphorylation of p210Bcr-Abl (IC50 = 5 nM) and the kinase activity of purified recombinant Abl tyrosine kinase (IC50 = 2.2 nM). Incubation of K562 cells with PD180970 resulted in cell death. PD180970 is among the most potent inhibitors of the p210Bcr-Abl tyrosine kinase, which is present in almost all cases of human chronic myelogenous leukemia. PD180970 is a promising candidate as a novel therapeutic agent for Bcr-Abl-positive leukemia.

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