LC-MS/MS method for determination of geldanamycin derivative GM-AMPL in rat plasma to support preclinical development.

@article{Li2013LCMSMSMF,
  title={LC-MS/MS method for determination of geldanamycin derivative GM-AMPL in rat plasma to support preclinical development.},
  author={Yanping Li and Lin-yan Gao and Kai-tong Li and Shuai Meng and Jian-hua Zhu and Dong Li and Jie Jin and Guang-zhi Shan and Zhuo-Rong Li},
  journal={Journal of chromatography. B, Analytical technologies in the biomedical and life sciences},
  year={2013},
  volume={912},
  pages={
          43-9
        }
}
  • Yanping Li, Lin-yan Gao, Zhuo-Rong Li
  • Published 2013
  • Chemistry, Biology
  • Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

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References

SHOWING 1-10 OF 25 REFERENCES
Metabolism of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) by murine and human hepatic preparations.
TLDR
In vitro metabolism of 17 AAG by mouse and human hepatic preparations was studied to characterize the enzymes responsible for 17AAG metabolism and the structures of the metabolites produced, implying that metabolite 2 is a diol and metabolite 6 is an epoxide.
Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) in CD2F1 mice1
TLDR
The plasma pharmacokinetics, tissue distribution, and urinary excretion of 17AAG after i.p. and oral delivery, and the concentrations of 17 AAG metabolites in plasma and tissue showed that the data were fitted best by a two-compartment, open, linear model.
Synthesis and biological activities of novel 17-aminogeldanamycin derivatives.
Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent
TLDR
In consideration of the potential for acute hepatotoxic reactions to GM, as well as to the other benzoquinoid ansamycins based upon structural analogy, additional pharmacological and therapeutic information is required to ascertain whether these compounds are viable candidates for clinical development.
A novel class of geldanamycin derivatives as HCV replication inhibitors targeting on Hsp90: synthesis, structure–activity relationships and anti-HCV activity in GS4.3 replicon cells
A novel class of geldanamycin (GA) derivatives as hepatitis C virus (HCV) replication inhibitors has been synthesized and their anti-HCV activities were evaluated in GS4.3 HCV replicon cells. Most of
Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 rats
TLDR
A 75 mg/kg dose of 17DMAG caused no changes in appearance, appetite, waste elimination, or survival of treated mice as compared to vehicle-treated controls and was best fit by a one-compartment open linear model.
Synthesis and Biological Evaluation of Heat-Shock Protein 90 Inhibitors: Geldanamycin Derivatives with Broad Antiviral Activities
TLDR
The 17-amino-17-demethoxygeldanamycin derivatives could be novel agents with potential antiviral activity and targeting heat-shock protein 90 could be a new antiviral approach that is not prone to the development of drug resistance.
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