In an effort to overcome the unavailability of cotylenin A (CN A), an anticancer agent and a stabilizer of protein-protein interactions (PPIs) mediated by 14-3-3 proteins, ISIR-050 was designed as a CN A mimic. The synthesis was accomplished via a semisynthetic approach starting from fusicoccin A. ISIR-050 showed interferon-α (IFNα)-dependent growth inhibitory activity and a PPI stabilization effect similar to those of CN A. The biochemical analysis suggested that ISIR-050 and CN A induce the same pharmacological response to IFNα-treated cancer cells and that 14-3-3 proteins play a role in the mode of action.
fusicoccin, 14-3-3 Protein, anticancer agent, cotylenin, protein–protein interaction
NCBI PubMed ID: 29398541Publication DOI: 10.1016/j.bmcl.2018.01.030Journal NLM ID: 9107377Publisher: Elsevier
Correspondence: Higuchi Y
Institutions: The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Japan, Compound Library Screening Center, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Japan, Cancer Center, Faculty of Medicine, Shimane University, Japan
Methods: NMR, cytotoxicity assay
Found