Department of Chemistry
Antagonizing STAT3 dimerization with a rhodium(III) complex
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.
antitumor agents, cytotoxicity, dimerization, protein-protein interactions, rhodium
Source Publication Title
Angewandte Chemie International Edition
Link to Publisher's Edition
Ma, Dik-Lung, Li-Juan Liu, Ka-Ho Leung, Yen-Ting Chen, Hai-Jing Zhong, Daniel Shiu-Hin Chan, Hui-Min David Wang, and Chung-Hang Leung. "Antagonizing STAT3 dimerization with a rhodium(III) complex." Angewandte Chemie International Edition 53.5 (2014): 9178-9182.