Indeno[1,2-b]indole derivatives as a novel class of potent human protein kinase CK2 inhibitors |
| |
| Authors: | Hundsdörfer Claas Hemmerling Hans-Jörg Götz Claudia Totzke Frank Bednarski Patrick Le Borgne Marc Jose Joachim |
| |
| Affiliation: | 1. Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Hittorfstraße 58-62, 48149 Münster, Germany;2. Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany;3. Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Gebäude 44, D-66424 Homburg/Saar, 66421 Homburg, Germany;4. ProQinase GmbH, Breisacher Str. 117, 79106 Freiburg, Germany;5. Institut für Pharmazie, Ernst-Moritz-Arndt-Universität Greifswald, Friedrich-Ludwig-Jahn-Straße 17, 17487 Greifswald, Germany;6. Institut des Sciences Pharmaceutiques et Biologiques, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France |
| |
| Abstract: | Herein we describe the synthesis and properties of indeno[1,2-b]indole derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 19 compounds was obtained using a convenient and straightforward synthesis protocol. The compounds were tested for inhibition of human protein kinase CK2, which was recombinantly expressed in Escherichia coli. New inhibitors with IC(50) in the micro- and sub-micromolar range were identified. Compound 4b (5-isopropyl-7,8-dihydroindeno[1,2-b]indole-9,10(5H,6H)-dione) inhibited human CK2 with an IC(50) of 0.11 μM and did not significantly inhibit 22 other human protein kinases, suggesting selectivity towards CK2. ATP-competitive inhibition by compound 4b was shown and a K(i) of 0.06 μM was determined. Our findings indicate that indeno[1,2-b]indoles are a promising starting point for further development and optimization of human protein kinase CK2 inhibitors. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
