Discovery of a Highly Selective STK16 Kinase Inhibitor

详细信息    查看全文

• 作者：Feiyang Liu ; Jinhua Wang ; Xingxing Yang ; Binhua Li ; Hong Wu ; Shuang Qi ; Cheng Chen ; Xiaochuan Liu ; Kailin Yu ; Wenchao Wang ; Zheng Zhao ; Aoli Wang ; Yongfei Chen ; Li Wang ; Nathanael S. Gray ; Jing Liu ; Xin Zhang ; Qingsong Liu
• 刊名：ACS Chemical Biology
• 出版年：2016
• 出版时间：June 17, 2016
• 年：2016
• 卷：11
• 期：6
• 页码：1537-1543
• 全文大小：577K
• 年卷期：0
• ISSN：1554-8937

文摘

STK16, a serine/threonine protein kinase, is ubiquitously expressed and is conserved among all eukaryotes. STK16 has been implicated to function in a variety of cellular processes such as VEGF and cargo secretion, but the pathways through which these effects are mediated remain to be elucidated. Through screening of our focused library of kinase inhibitors, we discovered a highly selective ATP competitive inhibitor, STK16-IN-1, which exhibits potent inhibitory activity against STK16 kinase (IC₅₀: 0.295 μM) with excellent selectivity across the kinome as assessed using the KinomeScan profiling assay (S score (1) = 0.0). In MCF-7 cells, treatment with STK16-IN-1 results in a reduction in cell number and accumulation of binucleated cells, which can be recapitulated by RNAi knockdown of STK16. Co-treatment of STK16-IN-1 with chemotherapeutics such as cisplatin, doxorubicin, colchicine, and paclitaxel results in a slight potentiation of the antiproliferative effects of the chemotherapeutics. STK16-IN-1 provides a useful tool compound for further elucidating the biological functions of STK16.