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 nontransformed cells, as well as selective inhibition of the biomarker GSK3 provides evidence that the compounds can affect the RSK2 target in cells.
A. Andreani, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, et al. (2011). Imidazo[2,1-b]thiazole guanylhydrazones as RSK2 inhibitors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 46, 4311-4323 [10.1016/j.ejmech.2011.07.001].
Imidazo[2,1-b]thiazole guanylhydrazones as RSK2 inhibitors
ANDREANI, ALDO;GRANAIOLA, MASSIMILIANO;LEONI, ALBERTO;LOCATELLI, ALESSANDRA;MORIGI, RITA;RAMBALDI, MIRELLA;VAROLI, LUCILLA;
2011
Abstract
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 nontransformed cells, as well as selective inhibition of the biomarker GSK3 provides evidence that the compounds can affect the RSK2 target in cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
