Liu Li-Juan, Wang Wanhe, Kang Tian-Shu, Liang Jia-Xin, Liu Chenfu, Kwong Daniel W J, Wong Vincent Kam Wai, Ma Dik-Lung, Leung Chung-Hang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Sci Rep. 2016 Nov 17;6:36044. doi: 10.1038/srep36044.
Targeting STAT5 is an appealing therapeutic strategy for the treatment of hematologic malignancies and inflammation. Here, we present the novel osmium(II) complex 1 as the first metal-based inhibitor of STAT5B dimerization. Complex 1 exhibited superior inhibitory activity against STAT5B DNA binding compared to STAT5A DNA binding. Moreover, 1 repressed STAT5B transcription and blocked STAT5B dimerization via binding to the STAT5B protein, thereby inhibiting STAT5B translocation to the nucleus. Furthermore, 1 was able to selectively inhibit STAT5B phosphorylation without affecting the expression level of STAT5B.
靶向信号转导和转录激活因子5（STAT5）是治疗血液系统恶性肿瘤和炎症的一种有吸引力的治疗策略。在此，我们展示了新型锇（II）配合物1作为首个基于金属的STAT5B二聚化抑制剂。与STAT5A的DNA结合相比，配合物1对STAT5B的DNA结合表现出更强的抑制活性。此外，1通过与STAT5B蛋白结合抑制STAT5B转录并阻断STAT5B二聚化，从而抑制STAT5B向细胞核的转运。此外，1能够选择性抑制STAT5B磷酸化，而不影响STAT5B的表达水平。
