title: Antagonizing STAT3 dimerization with a rhodium(III) complex.
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, 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.
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong (China). edmondma@hkbu.edu.hk.
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Liu
authors.forename: Ka-Ho
authors.initials: KH
authors.lastname: Leung
authors.forename: Yen-Ting
authors.initials: YT
authors.lastname: Chen
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Zhong
authors.forename: Daniel Shiu-Hin
authors.initials: DS
authors.lastname: Chan
authors.forename: Hui-Min David
authors.initials: HM
authors.lastname: Wang
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects*; D012238:Rhodium / Q000737:chemistry*; D050796:STAT3 Transcription Factor / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012238:Rhodium
keywords: antitumor agents; cytotoxicity; dimerization; protein-protein interactions; rhodium