Related Experiment Video
Updated: Oct 25, 2025
Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
In Vitro Metabolism Study of Seongsanamide A in Human Liver Microsomes Using Non-Targeted Metabolomics and
Zhexue Wu1, Geum Jin Kim2, So-Young Park3
1Mass Spectrometry Based Convergence Research Institute, Kyungpook National University, Daegu 41566, Korea.
Abstract:
Seongsanamide A is a bicyclic peptide with an isodityrosine residue discovered in Bacillus safensis KCTC 12796BP which exhibits anti-allergic activity in vitro and in vivo without significant cytotoxicity. The purpose of this study was to elucidate the in vitro metabolic pathway and potential for drug interactions of seongsanamide A in human liver microsomes using non-targeted metabolomics and feature-based molecular networking (FBMN) techniques. We identified four metabolites, and their structures were elucidated by interpretation of high-resolution tandem mass spectra. The primary metabolic pathway associated with seongsanamide A metabolism was hydroxylation and oxidative hydrolysis. A reaction phenotyping study was also performed using recombinant cytochrome P450 isoforms. CYP3A4 and CYP3A5 were identified as the major metabolic enzymes responsible for metabolite formation. Seongsanamide A did not inhibit the cytochrome P450 isoforms commonly involved in drug metabolism (IC50 > 10 µM). These results will contribute to further understanding the metabolism and drug interaction potential of various bicyclic peptides.
