CGP 57148, a Tyrosine Kinase Inhibitor, Inhibits the Growth of Cells Expressing BCR-ABL, TEL-ABL, and TEL-PDGFR Fusion Proteins

摘要: CGP 57148 is a compound of the 2-phenylaminopyrimidine class that selectively inhibits tyrosine kinase activity ABL and platelet-derived growth factor receptor (PDGFR) protein kinases. We previously showed kills p210BCR-ABL-expressing cells. To extend these observations, we evaluated ability to inhibit other activated kinases, including p185BCR-ABL TEL-ABL. In cell-based assays phosphorylation, inhibition was observed at concentrations similar reported for p210BCR-ABL. Consistent with in vitro profile this compound, cells expressing kinases inhibited absence exogenous factor. Growth also p185BCR-ABL-positive acute lymphocytic leukemia (ALL) cell line generated from Philadelphia chromosome-positive ALL patient. As PDGFR kinase, an TEL-PDGFR, are sensitive compound. Thus, may be useful treatment variety BCR-ABL-positive leukemias subset chronic myelomonocytic patients TEL-PDGFR fusion protein.