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The derivative CGP 41 251 had reduced PKC activity with an IC<jats:sub>50<\/jats:sub> of 50 nm but showed a high degree of selectivity when assayed for inhibition of cyclic AMP\u2010dependent protein kinase (IC<jats:sub>50<\/jats:sub>, 2.4 \u03bcm). 56 kinase (IC<jats:sub>50<\/jats:sub> 5.0 \u03bcm). and tyrosine\u2010kinase\u2010specific activity of epidermal growth factor receptor (IC<jats:sub>50<\/jats:sub> 3.0 \u03bcm). Staurosporine and CGP 41 251 exerted growth inhibition in the human bladder carcinoma line T\u201024, human promyelocytic leukemia line HL\u201060 and bovine corneal endothelial cells at concentrations which correlated well with <jats:italic>in vitro<\/jats:italic> PKC inhibition. In addition, both compounds inhibited the release of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> from human monocytes pre\u2010treated with 12\u2010O\u2010tetradecanoyl\u2010phorbol\u201013\u2010acetate at non\u2010toxic concentrations. <jats:italic>In vivo<\/jats:italic> anti\u2010tumor activity was examined in T\u201024 human bladder carcinoma xenografts in athymic nude mice. Tumor growth inhibition tests revealed significant anti\u2010tumor activity (2<jats:sub>p<\/jats:sub> &lt; 0.001) at 1\/10 of the maximum tolerated doses for both compounds. By contrast, a closely related derivative of staurosporine (CGP 42 700) was inactive at concentrations of over 100 \u03bcm in all <jats:italic>in vitro<\/jats:italic> enzyme and anti\u2010proliferative assays as well as in animal tumor models. Our data suggest an association between PKC inhibition and anti\u2010proliferative and anti\u2010tumor activity.<\/jats:p>","DOI":"10.1002\/ijc.2910430519","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T21:45:49Z","timestamp":1171921549000},"page":"851-856","source":"Crossref","is-referenced-by-count":323,"title":["A derivative of staurosporine (CGP 41 251) shows selectivity for protein kinase C inhibition and <i>In vitro<\/i> anti\u2010proliferative as well as <i>In vivo<\/i> anti\u2010tumor activity"],"prefix":"10.1002","volume":"43","author":[{"given":"Thomas","family":"Meyer","sequence":"first","affiliation":[]},{"given":"Urs","family":"Regenass","sequence":"additional","affiliation":[]},{"given":"Doriano","family":"Fabbro","sequence":"additional","affiliation":[]},{"given":"Enrica","family":"Alteri","sequence":"additional","affiliation":[]},{"given":"Johannes","family":"R\u00f6usel","sequence":"additional","affiliation":[]},{"given":"Marcel","family":"M\u00f6ller","sequence":"additional","affiliation":[]},{"given":"Giorgio","family":"Caravatti","sequence":"additional","affiliation":[]},{"given":"Alex","family":"Matter","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2006,7,17]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"287","article-title":"Altered subcellular distribution of protein kinase C (a phorbol ester receptor). 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