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http://dx.doi.org/10.5012/bkcs.2011.32.5.1709

A Highly Selective Staurosporine Derivative Designed by a New Selectivity Filter  

El-Deeb, Ibrahim M. (Center for Biomaterials, Korea Institute of Science and Technology)
Jung, Su-Jin (Department of Chemistry, Korea University)
Park, Byung-Sun (Center for Biomaterials, Korea Institute of Science and Technology)
Yoo, Young-Jun (Center for Biomaterials, Korea Institute of Science and Technology)
Choi, Ki-Hang (Department of Chemistry, Korea University)
Yang, Young-Mok (Department of Pathology, School of Medicine, Konkuk University)
Lee, Sang-Woo (Department of Chemistry, Kwangwoon University)
Kim, In-Tae (Department of Chemistry, Kwangwoon University)
Han, Dong-Keun (Center for Biomaterials, Korea Institute of Science and Technology)
Lee, So-Ha (Center for Biomaterials, Korea Institute of Science and Technology)
Publication Information
Bulletin of the Korean Chemical Society / v.32, no.5, 2011 , pp. 1709-1714 More about this Journal
Abstract
KIST301135 was semi-synthetically prepared by the reaction of Staurosporine with triphosgene in anhydrous dichloromethane. The structure of KIST301135 was confirmed by $^1H$ NMR, $^{13}C$ NMR, and high resolution mass spectrum. KIST301135 was initially tested in a single dose duplicate mode at a concentration of 20 nM over a panel of 53 kinases against Staurosporine as a positive control. KIST301135 has showed inhibitions above 75% in only 2 kinases (FLT3 and JAK3 kinases) of the 53 tested kinases, while Staurosporine has showed inhibitions above 80% in about 62% of the tested kinases. KIST301135 was retested at a 5-dose testing mode over the 9 kinases inhibited by percentages over 20 at the single dose testing in order to determine its $IC_{50}$ values. KIST301135 has shown much improved kinase inhibitory selectivity relative to Staurosporine in its potency at JAK3 kinase and CAMK2b kinase.
Keywords
Staurosporine derivative; Selectivity filter; Kinase selectivity; Cancer;
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