Premium
Antagonizing STAT3 Dimerization with a Rhodium(III) Complex
Author(s) -
Ma DikLung,
Liu LiJuan,
Leung KaHo,
Chen YenTing,
Zhong HaiJing,
Chan Daniel ShiuHin,
Wang HuiMin David,
Leung ChungHang
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201404686
Subject(s) - rhodium , iridium , chemistry , stat3 , in vivo , ruthenium , activator (genetics) , stat protein , platinum , stereochemistry , phosphorylation , cancer research , combinatorial chemistry , catalysis , biochemistry , medicine , biology , gene , microbiology and biotechnology
Kinetically inert metal complexes have arisen as promising alternatives to existing platinum and ruthenium chemotherapeutics. Reported herein, to our knowledge, is the first example of a substitutionally inert, Group 9 organometallic compound as a direct inhibitor of signal transducer and activator of transcription 3 (STAT3) dimerization. From a series of cyclometalated rhodium(III) and iridium(III) complexes, a rhodium(III) complex emerged as a potent inhibitor of STAT3 that targeted the SH2 domain and inhibited STAT3 phosphorylation and dimerization. Significantly, the complex exhibited potent anti‐tumor activities in an in vivo mouse xenograft model of melanoma. This study demonstrates that rhodium complexes may be developed as effective STAT3 inhibitors with potent anti‐tumor activity.