Epidithiodiketopiperazine as a pharmacophore for protein lysine methyltransferase G9a inhibitors: reducing cytotoxicity by structural simplification.

Basic Information

ID: ALA2311332

Journal: Bioorg Med Chem Lett

Title: Epidithiodiketopiperazine as a pharmacophore for protein lysine methyltransferase G9a inhibitors: reducing cytotoxicity by structural simplification.

Authors: Fujishiro S, Dodo K, Iwasa E, Teng Y, Sohtome Y, Hamashima Y, Ito A, Yoshida M, Sodeoka M.

Abstract: Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibitor structure based on structure-activity relationship (SAR) studies on chaetocin derivatives. The simple derivative PS-ETP-1 (14) was found to be a potent G9a inhibitor with greatly reduced cytotoxicity.

CiteXplore: 23266120

DOI: 10.1016/j.bmcl.2012.11.087

Patent ID: ┄