Document Type

Journal Article

Department/Unit

Department of Chemistry

Title

Antagonizing STAT3 dimerization with a rhodium(III) complex

Language

English

Abstract

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, Group9 organometallic compound as a direct inhibitor of signal transducer and activator of transcription3 (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 invivo mouse xenograft model of melanoma. This study demonstrates that rhodium complexes may be developed as effective STAT3 inhibitors with potent anti-tumor activity. Saving your skin: A rhodium(III) complex is the first example of a substitutionally inert, Group9 organometallic compound which serves as a direct inhibitor of the signal transducer and activator of transcription3 (STAT3) dimerization. The rhodium(III) complex inhibited STAT3 activity invitro and invivo and showed potent and selective anticancer activity against melanoma cell lines and melanoma xenografts in an invivo mouse model. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Keywords

antitumor agents, cytotoxicity, dimerization, protein-protein interactions, rhodium

Publication Date

2014

Source Publication Title

Angewandte Chemie International Edition

Volume

53

Issue

5

Start Page

9178

End Page

9182

Publisher

Wiley-VCH Verlag

DOI

10.1002/anie.201404686

Link to Publisher's Edition

http://dx.doi.org/10.1002/anie.201404686

ISSN (print)

14337851

ISSN (electronic)

15213773

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