In Silico Discovery of JMJD6 Inhibitors for Cancer Treatment

  • ACS Med Chem Lett. 2019 Nov 19;10(12):1609-1613. doi: 10.1021/acsmedchemlett.9b00264.
Ting Ran  1  2 ,  Rongquan Xiao  1 ,  Qixuan Huang  1 ,  Haoliang Yuan  3 ,  Tao Lu  4 ,  Wen Liu  1
Affiliations
  • 1. Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian 361102, China.
  • 2. Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361105, China.
  • 3. Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
  • 4. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
PMID: 31857835 DOI: 10.1021/acsmedchemlett.9b00264
Abstract

The 2-oxoglutarate (2OG)-dependent oxygenase JMJD6 is emerging as a potential Anticancer target, but its inhibitors have not been reported so far. In this study, we reported an in silico protocol to discover JMJD6 inhibitors targeting the druggable 2OG-binding site. Following this protocol, one compound, which we named as WL12, was found to be able to inhibit JMJD6 enzymatic activity and JMJD6-dependent cell proliferation. To our best knowledge, this is the first case in drug discovery targeting JMJD6.