He Wu, Zhou Bin, Liu Weijia, Zhang Meizi, Shen Zhenhua, Han Zhifu, Jiang Qingwei, Yang Qinghua, Song Chuanjun, Wang Ruiyong, Niu Tianhui, Han Shengna, Zhang Lirong, Wu Jie, Guo Feima, Zhao Renbin, Yu Wenquan, Chai Jijie, Chang Junbiao
College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.
School of Life Sciences, Tsinghua University , Beijing 100084, PR China.
J Med Chem. 2015 Sep 24;58(18):7341-8. doi: 10.1021/acs.jmedchem.5b00702. Epub 2015 Sep 3.
N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.
N-(5-氯-2,4-二羟基苯基)-1-苯基环丁烷甲酰胺（N-CDPCB，1a）被发现是脂肪量和肥胖相关蛋白（FTO）的一种抑制剂。人FTO与1a的晶体结构揭示了FTO抑制剂的一个新结合位点，并确定了FTO识别该抑制剂的分子基础。新结合位点的确定为进一步开发选择性和强效的FTO抑制剂提供了新机会，有望为肥胖或肥胖相关疾病的治疗提供有关新治疗靶点的信息。
