A highly selective staurosporine derivative designed by a new selectivity filter

Ibrahim M. El-Deeb; Su Jin Jung; Byung Sun Park; Young Jun Yoo; Kihang Choi; Young Mok Yang; Sang Woo Lee; Tae Kim; Dong Keun Han; So Ha Lee

doi:10.5012/bkcs.2011.32.5.1709

A highly selective staurosporine derivative designed by a new selectivity filter

Ibrahim M. El-Deeb, Su Jin Jung, Byung Sun Park, Young Jun Yoo, Kihang Choi, Young Mok Yang, Sang Woo Lee, Tae Kim, Dong Keun Han, So Ha Lee

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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 IC50 values. KIST301135 has shown much improved kinase inhibitory selectivity relative to Staurosporine in its potency at JAK3 kinase and CAMK2b kinase.

Original language	English
Pages (from-to)	1709-1714
Number of pages	6
Journal	Bulletin of the Korean Chemical Society
Volume	32
Issue number	5
DOIs	https://doi.org/10.5012/bkcs.2011.32.5.1709
Publication status	Published - 2011 May 20

Keywords

Cancer
Kinase selectivity
Selectivity filter
Staurosporine derivative

ASJC Scopus subject areas

General Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.5012/bkcs.2011.32.5.1709

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title = "A highly selective staurosporine derivative designed by a new selectivity filter",

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 IC50 values. KIST301135 has shown much improved kinase inhibitory selectivity relative to Staurosporine in its potency at JAK3 kinase and CAMK2b kinase.",

keywords = "Cancer, Kinase selectivity, Selectivity filter, Staurosporine derivative",

author = "El-Deeb, {Ibrahim M.} and Jung, {Su Jin} and Park, {Byung Sun} and Yoo, {Young Jun} and Kihang Choi and Yang, {Young Mok} and Lee, {Sang Woo} and Tae Kim and Han, {Dong Keun} and Lee, {So Ha}",

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AU - El-Deeb, Ibrahim M.

AU - Jung, Su Jin

AU - Park, Byung Sun

AU - Yoo, Young Jun

AU - Choi, Kihang

AU - Yang, Young Mok

AU - Lee, Sang Woo

AU - Kim, Tae

AU - Han, Dong Keun

AU - Lee, So Ha

PY - 2011/5/20

Y1 - 2011/5/20

N2 - 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 IC50 values. KIST301135 has shown much improved kinase inhibitory selectivity relative to Staurosporine in its potency at JAK3 kinase and CAMK2b kinase.

AB - 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 IC50 values. KIST301135 has shown much improved kinase inhibitory selectivity relative to Staurosporine in its potency at JAK3 kinase and CAMK2b kinase.

KW - Cancer

KW - Kinase selectivity

KW - Selectivity filter

KW - Staurosporine derivative

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A highly selective staurosporine derivative designed by a new selectivity filter

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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