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Gleevac - Essay Example

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Gleevec contains imatinib mesylate that is a tyrosine kinase inhibitor. Imatinib mesylate is a synthetic drug belonging to the 2-phenyl amino-pyrimidine (PAP) group (Zimmerman et al.,…
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Download file to see previous pages It has four pKa values; 1.52, 2.56, 3.73, 8.07, very soluble in buffers of PH 5.5 and slightly soluble in neutral/alkaline aqueous buffers. Gleevec recognizes the auto inhibitory conformation of the activation loop of the protein that regulates the kinase activity. The structure of inactive state is distinct between different kinases. It has a half-life of 15 hours and allows daily administration.
Gleevec is used to treat the chronic phase of CML though applications have been found in Advanced and blast crisis phases. Its efficacy has been found to reduce with phase progression.Most patients that don’t respond to gleevec are in advanced stages of CML at the initiation of treatment. Failure rate of imatinib in patient with chronic phase CML remains low(at less than 15%at 18 months) in patients who did not respond to interferon.
In the 1980’s and 90’s much skepticism prevailed first on the development of compounds with specificity among protein kinases. Secondly, the targeting of singular molecular defects seemed insufficient in the treatment of highly heterogeneous cancer [11]. Gazit in 1989 reported low molecular weight tyrosine kinase inhibitors with selective activity towards EGFR. These inhibitors were called tyrophostins. Tyrophostins were useful in selective antiproliferation agents for proliferative diseases caused by hyperactivity of protein tyrosine kinases. Though tyrophostins were not clinically developed, they provided the proof of the principle of selective inhibition of tyrosine kinases by using small molecules [16]. Subsequently 2 phenylaminopyrimidines were reported as selective inhibitors for protein kinases C (PKC), Abelson (ABL) and platelet derived growth factor receptor (PDGFR) kinases [3]. Tyrosine kinases mediate many of the signaling pathways by which cancer cells promote their proliferation and survival. They control cellular function and are thought to be too similar to be inhibited in-vivo [15]. Overall imatinib shows ...Download file to see next pagesRead More
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