State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macao, P. R. China.
Department of Chemistry, Hong Kong Baptist University , Kowloon Tong, Hong Kong, P. R. China.
J Med Chem. 2016 Apr 28;59(8):4026-31. doi: 10.1021/acs.jmedchem.6b00112. Epub 2016 Apr 14.
The novel iridium(III) complex 1 was verified as a potent inhibitor of the TNF-α-TNFR protein-protein interaction in vitro and in cellulo. The iridium(III) center plays a critical role in organizing the structure of the bioactive metal complex, as the isolated ligands were found to be completely inactive. Both iridium enantiomers inhibited TNF-α-induced NF-κB activity and TNF-α-TNFR binding. 1 represents a promising scaffold for the further development of more potent organometallic TNF-α inhibitors.
新型铱(III)配合物 1 被证实为体外和细胞内 TNF-α-TNFR 蛋白-蛋白相互作用的有效抑制剂。铱(III)中心在组织生物活性金属配合物的结构方面起着关键作用，因为分离的配体被发现完全没有活性。两种铱对映体均抑制 TNF-α 诱导的 NF-κB 活性和 TNF-α-TNFR 结合。1 代表了进一步开发更有效的有机金属 TNF-α 抑制剂的有前途的支架。
