Rui Su, Lei Dong, Yangchan Li, Min Gao, Li Han, Mark Wunderlich, Xiaolan Deng, Hongzhi Li, Yue Huang, Lei Gao, Chenying Li, Zhicong Zhao, Sean Robinson, Brandon Tan, Ying Qing, Xi Qin, Emily Prince, Jun Xie, Hanjun Qin, Wei Li, Chao Shen, Jie Sun, Prakash Kulkarni, Hengyou Weng, Huilin Huang, Zhenhua Chen, Bin Zhang, Xiwei Wu, Mark J Olsen, Markus Müschen, Guido Marcucci, Ravi Salgia, Ling Li, Amir T Fathi, Zejuan Li, James C Mulloy, Minjie Wei, David Horne, Jianjun Chen
Fat mass and obesity-associated protein (FTO), an RNA N6 -methyladenosine (m6 A) demethylase, plays oncogenic roles in various cancers, presenting an opportunity for the development of effective targeted therapeutics. Here, we report two potent small-molecule FTO inhibitors that exhibit strong anti-tumor effects in multiple types of cancers. We show that genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially LILRB4...
July 13, 2020: Cancer Cell