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Overview
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Background
OSI-420 is the major metabolite of OSI-774(erlotinib) which is a small molecule, orally active, potent, and selective inhibitor of EGFR tyrosine kinase with an IC50 value of 2nM[1,2].OSI-420 is the active metabolite of OSI-774(erlotinib) which selectively inhibits the EGFR tyrosine kinase and prevents autophosphorylation by competing with adenosine triphosphate (ATP) for its binding site on the intracellular domain of EGFR. In addition, erlotinib, is metabolized to produce ATP, has been found to be selective for EGFR and lead to the induction of apoptosis by inducing the disruption of mitochondrial effect on loss of mitochondrial membrane potential and release of cytocrome c [1, 2].
[1] Zhang W1, Siu LL, Moore MJ, Chen EX.Simultaneous determination of OSI-774 and its major metabolite OSI-420 in human plasma by using HPLC with UV detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jan 5;814(1):143-7.
[2] Bonomi P. Erlotinib: a new therapeutic approach for non-small cell lung cancer.Expert Opin Investig Drugs. 2003 Aug;12(8):1395-401.
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