Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.

@article{Schindler2000StructuralMF,
  title={Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.},
  author={Thomas E. Schindler and William G. Bornmann and Patricia Pellicena and W. Todd Miller and Bayard Clarkson and John Kuriyan},
  journal={Science},
  year={2000},
  volume={289 5486},
  pages={
          1938-42
        }
}
The inadvertent activation of the Abelson tyrosine kinase (Abl) causes chronic myelogenous leukemia (CML. [...] Key Result Critical to the binding of STI-571 is the adoption by the kinase of an inactive conformation, in which a centrally located "activation loop" is not phosphorylated. The conformation of this loop is distinct from that in active protein kinases, as well as in the inactive form of the closely related Src kinases. These results suggest that compounds that exploit the distinctive inactivation…Expand
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  • Biology, Medicine
  • Biochemical and biophysical research communications
  • 2003
TLDR
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Breakthroughs and Views STI-571: an anticancer protein-tyrosine kinase inhibitor q
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STI-571 (imatinib, Gleevec, Glivec, CGP 57148) is an inhibitor of the Abl group of protein-tyrosine kinases, which results from the fusion of the BCR and ABL genes that result from the reciprocal chromosomal translocation that forms the Philadelphia chromosome. Expand
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Urea derivatives, structurally related to the therapeutic agent STI571, have been identified, which potently inhibit the tyrosine kinase activity of recombinant Abl, and it was possible to differentiate between c-Abl and PDGFR kinase inhibition, with compound 22 being selective towards Abl and 23 selective for PDG FR. Expand
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Functional studies coupled with structural analysis define a myristoyl/phosphotyrosine switch in c-Abl that regulates docking and accessibility of the SH2 domain and provides new insights into the mechanism of action of STI-571. Expand
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