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

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

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

doi

10.1016/j.bmcl.2012.11.087

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

733-6

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)01539-9

journal_volume

23

pub_type

杂志文章

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