872373-39-2Relevant academic research and scientific papers
Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators
Li, Ridong,Ning, Xianling,Zhou, Shuo,Lin, Zhiqiang,Wu, Xingyu,Chen, Hong,Bai, Xinyu,Wang, Xin,Ge, Zemei,Li, Runtao,Yin, Yuxin
, p. 48 - 65 (2017/11/23)
Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti-proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 μM to 0.81 μM against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies.
α-Mercaptoketone based histone deacetylase inhibitors
Wash, Paul L.,Hoffman, Timothy Z.,Wiley, Brandon M.,Bonnefous, Celine,Smith, Nicholas D.,Sertic, Michael S.,Lawrence, Charles M.,Symons, Kent T.,Nguyen, Phan-Manh,Lustig, Kevin D.,Guo, Xin,Annable, Tami,Noble, Stewart A.,Hager, Jeffrey H.,Hassig, Christian A.,Malecha, James W.
scheme or table, p. 6482 - 6485 (2009/10/01)
In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel α-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, α-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo.
