Small molecule inhibitor targeting the DNA-binding domain of STAT3 suppresses tumor growth and STAT3

• 作 者: WeiHuang[1]ZizhengDong[2]YifanChen[2]FangWang[2]ChaoWang[2]HuiPeng[2]YantaoHe[3]GiaoHangoc[4]KarenPollok[5]GeorgeSandusky[6]Xin-YuanFu[7]HalBroxmeyer[7]Zhong-YinZhang[8]Jing-YuanLiu[9]Jian-TingZhang[1
• 机 构: State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking Univer
• 出 处: 2015医学前沿论坛暨第十四届全国肿瘤药理与化疗学术会议
• 发表日期: 2015年期

　　Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and plays important roles in multiple aspects of cancer aggressiveness.Thus, targeting STAT3 promises to be an attractive strategy for treatment of advanced metastatic tumors.Although many STAT3 inhibitors targeting the SH2 domain have been reported, none has moved into clinical studies.Targeting the DNA-binding domain (DBD) of STAT3, however, has been avoided due to its "undruggable" nature and potentially limited selectivity.In a previous study, we reported an improved in-silico approach targeting the DBD of STAT3 that resulted in a small molecule STAT3 inhibitor (inS3-54).Further studies, however, showed that inS3-54 has off-target effect although it is selective to STAT3 over STAT1 as determined by STAT3-dependent colony formation assay.