Imidazo[2,1-b]thiazole guanylhydrazones as RSK2 inhibitors [1]

被引：75

作者：

Andreani, Aldo ^{[1
]}

Granaiola, Massimiliano ^{[1
]}

Leoni, Alberto ^{[1
]}

Locatelli, Alessandra ^{[1
]}

Morigi, Rita ^{[1
]}

Rambaldi, Mirella ^{[1
]}

Varoli, Lucilla ^{[1
]}

Lannigan, Deborah ^{[2
]}

Smith, Jeff ^{[3
]}

Scudiero, Dominic ^{[4
]}

Kondapaka, Sudhir ^{[5
]}

Shoemaker, Robert H. ^{[5
]}

机构：

[1] Univ Bologna, Dipartimento Sci Farmaceut, I-40126 Bologna, Italy

[2] Univ Virginia, Dept Microbiol, Ctr Cell Signaling, Charlottesville, VA 22908 USA

[3] Univ Virginia, Dept Pathol, Ctr Cell Signaling, Charlottesville, VA 22908 USA

[4] NCI, SAIC Frederick, Frederick, MD 21702 USA

[5] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 09期

关键词：

Imidazo[2,1-b]thiazole; Guanylhydrazones; Antitumor activity; RSK2; POTENTIAL ANTITUMOR AGENTS; TERMINAL KINASE DOMAIN; S6; KINASE; IN-VIVO; IDENTIFICATION; CELLS;

D O I：

10.1016/j.ejmech.2011.07.001

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The activity of a series of imidazo[2,1-b]thiazole guanylhydrazones as inhibitors of p90 ribosomal S6 kinase 2 (RSK2) is described. It was found that a small subset of compounds show both potent inhibition of RSK2 kinase activity and tumor cell growth in vitro. Detailed study of one of the most active compounds indicates a high degree of selectivity for inhibition of RSK2 compared to a spectrum of other related kinases. Selective inhibition of the MCF-7 breast tumor cell line compared to MCF-10A non-transformed cells, as well as selective inhibition of the biomarker GSK3 provides evidence that the compounds can affect the RSK2 target in cells. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：4311 / 4323

页数：13

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