Gleevec® Targets the Cause of CML

• Gleevec is a specific and potent inhibitor of a small family of tyrosine kinases, including Bcr-

Abl.1,2

– Gleevec acts specifically by blocking the binding site for ATP in the Abl kinase, thereby

preventing the phosphorylation of tyrosine residues on substrate proteins.

– By inhibiting phosphorylation, Gleevec prevents the activation of signal transduction

pathways that induce the leukemic transformation to CML.

• Imatinib mesylate is not entirely selective for the Bcr-Abl tyrosine kinase; it also inhibits the

receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF),

Kit, and inhibits PDGF- and SCF-mediated cellular events.

References

1. Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561-566.

2. Gleevec® (imatinib mesylate) Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2003.