A Highly Selective Staurosporine Derivative Designed by a New Selectivity Filter
作者： Ibrahim M. El-Deeb , Su-Jin Jung , Byung-Sun Park , Young-Jun Yoo , Ki-Hang Choi
DOI: 10.5012/BKCS.2011.32.5.1709
关键词: Derivative (chemistry) 、 Potency 、 Dichloromethane 、 Kinase 、 Selectivity 、 Chemistry 、 Selectivity filter 、 Staurosporine 、 Chromatography 、 Triphosgene 、 Stereochemistry
摘要: KIST301135 was semi-synthetically prepared by the reaction of Staurosporine with triphosgene in anhydrous dichloromethane. The structure confirmed NMR, and high resolution mass spectrum. initially tested a single dose duplicate mode at concentration 20 nM over panel 53 kinases against as positive control. has showed inhibitions above 75% only 2 (FLT3 JAK3 kinases) kinases, while 80% about 62% kinases. retested 5-dose testing 9 inhibited percentages order to determine its values. shown much improved kinase inhibitory selectivity relative potency CAMK2b kinase.
koreascience.or.kr
elsevier.com参考文章(22)
Andreas Gescher, Analogs of staurosporine: potential anticancer drugs? General Pharmacology-the Vascular System. ,vol. 31, pp. 721- 728 ,(1998) , 10.1016/S0306-3623(98)00069-X
Titus J. Boggon, Yiqun Li, Paul W. Manley, Michael J. Eck, Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog Blood. ,vol. 106, pp. 996- 1002 ,(2005) , 10.1182/BLOOD-2005-02-0707
M ANDERSON, Calmodulin kinase signaling in heart: an intriguing candidate target for therapy of myocardial dysfunction and arrhythmias Pharmacology & Therapeutics. ,vol. 106, pp. 39- 55 ,(2005) , 10.1016/J.PHARMTHERA.2004.11.002
Timothy W. Corson, Nicholas Aberle, Craig M. Crews, Design and Applications of Bifunctional Small Molecules: Why Two Heads Are Better Than One ACS Chemical Biology. ,vol. 3, pp. 677- 692 ,(2008) , 10.1021/CB8001792
Thomas Force, Daniela S. Krause, Richard A. Van Etten, Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nature Reviews Cancer. ,vol. 7, pp. 332- 344 ,(2007) , 10.1038/NRC2106
Risto Kerkelä, Luanda Grazette, Rinat Yacobi, Cezar Iliescu, Richard Patten, Cara Beahm, Brian Walters, Sergei Shevtsov, Stéphanie Pesant, Fred J Clubb, Anthony Rosenzweig, Robert N Salomon, Richard A Van Etten, Joseph Alroy, Jean-Bernard Durand, Thomas Force, Cardiotoxicity of the cancer therapeutic agent imatinib mesylate Nature Medicine. ,vol. 12, pp. 908- 916 ,(2006) , 10.1038/NM1446
Ariel Fernández, Sridhar Maddipati, A priori inference of cross reactivity for drug-targeted kinases. Journal of Medicinal Chemistry. ,vol. 49, pp. 3092- 3100 ,(2006) , 10.1021/JM060163J
Alejandro Crespo, Ariel Fernández, Kinase packing defects as drug targets Drug Discovery Today. ,vol. 12, pp. 917- 923 ,(2007) , 10.1016/J.DRUDIS.2007.09.009
Miles A Fabian, William H Biggs, Daniel K Treiber, Corey E Atteridge, Mihai D Azimioara, Michael G Benedetti, Todd A Carter, Pietro Ciceri, Philip T Edeen, Mark Floyd, Julia M Ford, Margaret Galvin, Jay L Gerlach, Robert M Grotzfeld, Sanna Herrgard, Darren E Insko, Michael A Insko, Andiliy G Lai, Jean-Michel Lélias, Shamal A Mehta, Zdravko V Milanov, Anne Marie Velasco, Lisa M Wodicka, Hitesh K Patel, Patrick P Zarrinkar, David J Lockhart, A small molecule–kinase interaction map for clinical kinase inhibitors Nature Biotechnology. ,vol. 23, pp. 329- 336 ,(2005) , 10.1038/NBT1068
Baoguang Zhao, Michael J. Bower, Patrick J. McDevitt, Huizhen Zhao, Stephen T. Davis, Kyung O. Johanson, Susan M. Green, Nestor O. Concha, Bin-Bing S. Zhou, Structural basis for Chk1 inhibition by UCN-01. Journal of Biological Chemistry. ,vol. 277, pp. 46609- 46615 ,(2002) , 10.1074/JBC.M201233200