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Discovery of 4-anilino α-carbolines as novel Brk inhibitors.

Abstract：

:Dysregulation of cell signalling processes caused by an enhanced activity of protein kinases mainly contributes to cancer progression. Protein kinase inhibitors have been established as promising drugs that inhibit such overactive protein kinases in cancer cells. The formation of metastases, which makes a therapy difficult, remains a great challenge for cancer treatment. Recently, breast tumor kinase (Brk) was discovered as novel and interesting target for a cancer therapy because Brk participates in both cell dysregulation and metastasis. We discovered 4-anilino substituted α-carboline compounds as a novel class of highly active Brk inhibitors. In the current work, structure-activity relationships are discussed including docking results obtained for 4-anilino α-carbolines. A first profiling of selective kinase inhibition and a proof of concept for the antiproliferative effects is demonstrated. These results qualify the compounds as a promising class of novel antitumor agents.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Mahmoud KA,Krug M,Wersig T,Slynko I,Schächtele C,Totzke F,Sippl W,Hilgeroth A

doi

10.1016/j.bmcl.2014.03.002

subject

Has Abstract

pub_date

2014-04-15 00:00:00

pages

1948-51

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00218-2

journal_volume

24

pub_type

杂志文章

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