Clinical Development of 17-Allylamino, 17-Demethoxygeldanamycin
نویسندگان
چکیده
منابع مشابه
Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells.
Heat shock protein 90 (HSP90) inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), which is currently in phase II/phase III clinical trials, are promising new anticancer agents. Here, we explored acquired resistance to HSP90 inhibitors in glioblastoma (GB), a primary brain tumor with poor prognosis. GB cells were exposed continuously to increased 17-AAG concentrati...
متن کاملInhibition of telomerase activity by geldanamycin and 17-allylamino, 17-demethoxygeldanamycin in human melanoma cells.
As it has been demonstrated that the heat shock protein 90 (HSP90) is required for the assembly and activation of telomerase in human cells, we investigated the effect exerted by the ansamycin antibiotics geldanamycin (GA) and 17-allylamino,17-demethoxygeldanamycin (17-AAG), two well-known inhibitors of the HSP90 chaperone function, on telomerase activity in JR8 human melanoma cells. Using an a...
متن کاملPhase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies.
PURPOSE To study the toxicity and pharmacokinetic-pharmacodynamic profile of 17-allylamino, 17- demethoxygeldanamycin (17-AAG) and to recommend a dose for phase II trials. PATIENTS AND METHODS This was a phase I study examining a once-weekly dosing schedule of 17-AAG. Thirty patients with advanced malignancies were treated. RESULTS The highest dose level reached was 450 mg/m(2)/week. The do...
متن کاملPhase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer.
PURPOSE We determined the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLT) of 17-allylamino-17-demethoxygeldanamycin (17-AAG) when infused on days 1, 8, and 15 of a 28-day cycle in advanced solid tumor patients. We also characterized the pharmacokinetics of 17-AAG, its effect on chaperone and client proteins, and whether cytochrome P450 (CYP) 3A5 and NAD(P)H:quinone oxidoredu...
متن کاملMetabolism of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) by murine and human hepatic preparations.
17-(Allylamino)-17-demethoxygeldanamycin (17AAG), a compound that is proposed for clinical development, shares the ability of geldanamycin to bind to heat shock protein 90 and GRP94, thereby depleting cells of p185erbB2, mutant p53, and Raf-1. Urine and plasma from mice treated i.v. with 17AAG contained six materials with absorption spectra similar to that of 17AAG. Therefore, in vitro metaboli...
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ژورنال
عنوان ژورنال: Current Cancer Drug Targets
سال: 2003
ISSN: 1568-0096
DOI: 10.2174/1568009033481831