TY - JOUR
T1 - CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins
AU - Carroll, Martin
AU - Ohno-Jones, Sayuri
AU - Tamura, Shu
AU - Buchdunger, Elisabeth
AU - Zimmermann, Jürg
AU - Lydon, Nicholas B.
AU - Gilliland, D. Gary
AU - Druker, Brian J.
PY - 1997/12/15
Y1 - 1997/12/15
N2 - CGP 57148 is s compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the ABL and the platelet-derived growth factor receptor (PDGFR) protein tyrosine kinases. We previously showed that CGP 57148 selectively kills p210BCR-ABL-expressing cells. To extend these observations, we evaluated the ability of CGP 57148 to inhibit other activated ABL tyrosine kinases, including p185BCR-ABL and TEL- ABL in cell-based assays of ABL tyrosine phosphorylation, inhibition of ABL kinase activity was observed at concentrations similar to that reported for p210BCR-ABL. Consistent with the in vitro profile of this compound, the growth of cells expressing activated ABL protein tyrosine kinases was inhibited in the absence of exogenous growth factor. Growth inhibition was also observed with a p185BCR-ABL-positive acute lymphocytic leukemia (ALL) cell line generated from a Philadelphia chromosome-positive ALL patient. As CGP 57148 inhibits the PDGFR kinase, we also showed that cells expressing an activated PDGFR tyrosine kinase, TEL-PDGFR, are sensitive to this compound. Thus, this compound may be useful for the treatment of a variety of BCR-ABL- positive leukemias and for treatment of the subsets of chronic myelomonocytic leukemia patients with a TEL-PDGFR fusion protein.
AB - CGP 57148 is s compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the ABL and the platelet-derived growth factor receptor (PDGFR) protein tyrosine kinases. We previously showed that CGP 57148 selectively kills p210BCR-ABL-expressing cells. To extend these observations, we evaluated the ability of CGP 57148 to inhibit other activated ABL tyrosine kinases, including p185BCR-ABL and TEL- ABL in cell-based assays of ABL tyrosine phosphorylation, inhibition of ABL kinase activity was observed at concentrations similar to that reported for p210BCR-ABL. Consistent with the in vitro profile of this compound, the growth of cells expressing activated ABL protein tyrosine kinases was inhibited in the absence of exogenous growth factor. Growth inhibition was also observed with a p185BCR-ABL-positive acute lymphocytic leukemia (ALL) cell line generated from a Philadelphia chromosome-positive ALL patient. As CGP 57148 inhibits the PDGFR kinase, we also showed that cells expressing an activated PDGFR tyrosine kinase, TEL-PDGFR, are sensitive to this compound. Thus, this compound may be useful for the treatment of a variety of BCR-ABL- positive leukemias and for treatment of the subsets of chronic myelomonocytic leukemia patients with a TEL-PDGFR fusion protein.
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U2 - 10.1182/blood.v90.12.4947.4947_4947_4952
DO - 10.1182/blood.v90.12.4947.4947_4947_4952
M3 - Article
C2 - 9389713
AN - SCOPUS:0031454003
SN - 0006-4971
VL - 90
SP - 4947
EP - 4952
JO - Blood
JF - Blood
IS - 12
ER -