2. Academic Validation
  3. Computational discovery and biological evaluation of novel inhibitors targeting histone-lysine N-methyltransferase SET7

Computational discovery and biological evaluation of novel inhibitors targeting histone-lysine N-methyltransferase SET7

  • Bioorg Med Chem. 2020 Apr 1;28(7):115372. doi: 10.1016/j.bmc.2020.115372.
Wenjian Min 1,  Zeng Hou 2,  Fang Zhang 1,  Shengnan Xie 1,  Kai Yuan 1,  Haojie Dong 1,  Liping Wang 1,  Lianwen Qi 3,  Cheng Luo 2,  Hong Ding 4,  Peng Yang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
  • 2 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.
  • 3 State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
  • 4 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: hding@simm.ac.cn.
  • 5 State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: pengyang@cpu.edu.cn.
PMID: 32088124 DOI: 10.1016/j.bmc.2020.115372
Abstract

Histone-lysine N-methyltransferase SET7 emerged as a potential target for multiple cancers. In a virtual screening program used to explore new and potent inhibitors of SET7, compound 16 was discovered as a top hit with an IC50 value of 6.02 μM. A further similarity search afforded a new compound 23, which exhibited better activity against SET7 with an IC50 value of 1.96 μM. Importantly, compound 23 selectively inhibited the proliferation of MV4-11 cells. Comprehensively, compound 23 can serve as a lead for further identification and development of more potent SET7 inhibitors.

Keywords

Histone methylation; Lysine methyltransferase; SET7; Small-molecule inhibitor; Virtual screening.

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