Toxicity, Pharmacokinetics, and Gut Microbiome of Oral Administration of Sesterterpene MHO7 Derived from a Marine Fungus.

ABSTRACT: Sesterterpene MHO7 derived from mangrove fungus is a novel estrogen receptor degrader for the treatment of breast cancer. To explore its safety and pharmacokinetics in vivo, Log P/D values, stability in simulated gastric/intestinal (SGF/SIF), toxicity, and pharmacokinetics studies were carried mainly by liquid chromatography technique coupled with tandem mass spectrometry (LC-MS/MS) method in mice, and the effect of MHO7 on mice gut microbiota at different time points was revealed by 16S rRNA sequencing. Log P/D values ranged 0.93-2.48, and the compound in SGF and SIF is stable under the concentration of 5 mM·L-1. The maximum tolerance dose (MTD) of oral administration in mice was 2400 mg·kg-1. The main pharmacokinetics parameters were as following: Cmax of 1.38 μg·mL-1, Tmax of 8 h, a hal

SUBMITTER: Tian W 

PROVIDER: S-EPMC6950057 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature