In Silico Discovery of JMJD6 Inhibitors for Cancer Treatment

Ting Ran; Rongquan Xiao; Qixuan Huang; Haoliang Yuan; Tao Lu; Wen Liu

doi:10.1021/acsmedchemlett.9b00264

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. eCollection 2019 Dec 12.

Authors

Ting Ran^{1

2}, Rongquan Xiao¹, Qixuan Huang¹, Haoliang Yuan³, Tao Lu⁴, Wen Liu¹

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.

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.