A series of pyrazolo[3,4-d]pyrimidines, previously found to be Src inhibitors, was tested for their ability to inhibit proliferation of three Bcr-Abl-pos. human leukemia cell lines (K-562, KU-812, and MEG-01), on the basis of the exptl. evidence that various Src inhibitors are also active against Bcr-Abl kinase (the so called dual Src/Abl inhibitors). They reduce Bcr-Abl tyrosine phosphorylation and promote apoptosis of the Bcr-Abl-expressing cells. A cell-free enzymic assay on isolated c-Abl confirmed that such compds. directly inhibit Abl activity. Finally, mol. modeling simulations were also performed to hypothesize the binding mode of the compds. into the Abl binding site.

Inhibition of Bcr-Abl Phosphorylation and Induction of Apoptosis by Pyrazolo[3,4-d]pyrimidines in Human Leukemia Cells

BRULLO, CHIARA;SCHENONE, SILVIA;
2007-01-01

Abstract

A series of pyrazolo[3,4-d]pyrimidines, previously found to be Src inhibitors, was tested for their ability to inhibit proliferation of three Bcr-Abl-pos. human leukemia cell lines (K-562, KU-812, and MEG-01), on the basis of the exptl. evidence that various Src inhibitors are also active against Bcr-Abl kinase (the so called dual Src/Abl inhibitors). They reduce Bcr-Abl tyrosine phosphorylation and promote apoptosis of the Bcr-Abl-expressing cells. A cell-free enzymic assay on isolated c-Abl confirmed that such compds. directly inhibit Abl activity. Finally, mol. modeling simulations were also performed to hypothesize the binding mode of the compds. into the Abl binding site.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/265270
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