Antagonizing STAT3 dimerization with a rhodium(III) complex

Edmond Dik Lung MA, Li Juan Liu, Ka Ho Leung, Yen Ting Chen, Hai Jing Zhong, Daniel Shiu Hin Chan, Hui Min David Wang, Chung Hang Leung

Research output: Contribution to journalArticlepeer-review

101 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9178-9182
Number of pages5
JournalAngewandte Chemie. International Edition
Volume53
Issue number35
DOIs
Publication statusPublished - 25 Aug 2014

Scopus Subject Areas

  • Catalysis
  • Chemistry(all)

User-Defined Keywords

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

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