Indeno[1,2-b]indole derivatives as a novel class of potent human protein kinase CK2 inhibitors

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• 作者：Claas Hundsdö ; rfer^a ; Hans-Jö ; rg Hemmerling^b ; Claudia Gö ; tz^c ; Frank Totzke^d ; Patrick Bednarski^e ; Marc Le Borgne^f ; Joachim Jose^a ; ^{joachim.jose@uni-muenster.de}
• 关键词：DGOKKNPUISUUGY-UHFFFAOYSA-N
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：1 April, 2012
• 年：2012
• 卷：20
• 期：7
• 页码：2282-2289
• 全文大小：512 K

文摘

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 IC₅₀ 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 IC₅₀ of 0.11 ¦ÌM 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 ¦ÌM 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.