WEEKLY 17 ALLYLAMINO 17 DEMETHOXYGELDANAMYCIN

$0M01FY2000RRNIH

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

17-Allylamino, 17-demethoxygeldanamycin (17AAG) is an ansamycin benzoquinone antibiotic analogue of geldanamycin and herbimycin A. It is thought that the growth inhibitory activity of 17AAG is related to its ability to downregulate, although the specific protein or proteins, which are downregulated and lead to tumor growth inhibition are unknown. 17AAG has undergone extensive preclinical characterization, including definition of its pharmacokinetics in mice and its metabolism in mice and by murine and human hepatic preparations. This investigation will determine the maximum tolerated dose of 17AAG, the toxicities of this agent as well as its pharmacokinetics and pharmacodynamics.

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