Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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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)
  • Received : 2011.01.18
  • Accepted : 2011.03.07
  • Published : 2011.05.20
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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.

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References

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