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HowdoesCrizotinibpowderworks
2.HowdoesCrizotinibpowderworks?
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Crizotinib powder has an aminopyridine structure, and functions as a protein kinase inhibitor by competitive binding within the ATP-binding pocket of target kinases. About 4% of patients with non-small cell lung carcinoma have a chromosomal rearrangement that generates a fusion gene between EML4 (‘echinoderm microtubule-associated protein-like 4’) and ALK (‘anaplastic lymphoma kinase’), which results in constitutive kinase activity that contributes to carcinogenesis and seems to drive the malignant phenotype.The kinase activity of the fusion protein is inhibited by Crizotinib powder. Patients with this gene fusion are typically younger non-smokers who do not have mutations in either the epidermal growth factor receptor gene (EGFR) or in the K-Ras gene. The number of new cases of ALK-fusion NSLC is about 9,000 per year in the U.S. and about 45,000 worldwide.
ALK mutations are thought to be important in driving the malignant phenotype in about 15% of cases of neuroblastoma, a rare form of peripheral nervous system cancer that occurs almost exclusively in very young children.
Crizotinib powder inhibits the c-Met/Hepatocyte growth factor receptor (HGFR) tyrosine kinase, which is involved in the oncogenesis of a number of other histological forms of malignant neoplasms.
Crizotinib powder is currently thought to exert its effects through modulation of the growth, migration, and invasion of malignant cells. Other studies suggest that Crizotinib powder might also act via inhibition of angiogenesis in malignant tumors.
In order to get chiral 1-phenylethanol derivative, Liang and co-workers have used several microorganism for efficient reduction the ketone towards intermediate. Other groups tried to increase the efficiency and selectivity towards the chiral intermediate by using similar approaches. A fit-for-purpose route published by Koning and co-workers from Pfizer revels the strategy for producing the racemic alcohol by traditional NaBH4 reduction, followed by acetylation, resolution mediated by PLE and Mitsunobu inversion towards the required enantiomer.
Lipases are always the first option when thinking about obtaining highly enantiomeric pure chiral alcohols by kinetic resolutions or dynamic kinetic resolution (DKR) methods. Furthermore, lipases can be combined with racemization catalysts, namely palladium, iridium, vanadium or ruthenium complexes complexes. Unfortunately, to the best of our knowledge, no reports of lipases used on the kinetic or DKR of 1-(2,6-dichloro-3-fluorophenyl)ethanol were found.
In our continuous effort towards the development of biocatalytic protocols for the synthesis of intermediates for API synthesis, herein, we report our studies on the kinetic
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