A Highly Selective Staurosporine Derivative Designed by a New Selectivity Filter
A Highly Selective Staurosporine Derivative Designed by a New Selectivity Filter
Ibrahim M. El-Deeb(Department of Biomolecular Science, University of Science and Technology); 한동근(Korea Institute of Science and Technology); 김인태(관동대학교); Sang Woo Lee(Department of Chemistry, Kwangwoon University); 양영목(Konkuk University); 최기항(고려대학교); Young Jun Yoo(Korea Institute of Science and Technology); Byung Sun Park(Korea Institute of Science and Technology); Su Jin Jung(Korea University); 이소하(Korea Institute of Science & Technology)
32권 5호, 1709~1714쪽
초록
KIST301135 was semi-synthetically prepared by the reaction of Staurosporine with triphosgene in anhydrous dichloromethane. The structure of KIST301135 was confirmed by ^1H NMR, ^13C 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 IC50values. KIST301135 has shown much improved kinase inhibitory selectivity relative to Staurosporine in its potency at JAK3 kinase and CAMK2b kinase.
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, ^13C 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 IC50values. KIST301135 has shown much improved kinase inhibitory selectivity relative to Staurosporine in its potency at JAK3 kinase and CAMK2b kinase.
- 발행기관:
- 대한화학회
- 분류:
- 화학