2. Academic Validation
  3. Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays

Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays

  • Biomed Res Int. 2016;2016:7086390. doi: 10.1155/2016/7086390.
Fei Ye 1,  Weiyao Zhang 2,  Wenchao Lu 3,  Yiqian Xie 4,  Hao Jiang 3,  Jia Jin 2,  Cheng Luo 4
Affiliations

Affiliations

  • 1 College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China; Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, Hangzhou, China.
  • 2 College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
  • 3 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China.
  • 4 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
PMID: 27872854 DOI: 10.1155/2016/7086390
Abstract

Overexpression of coactivator associated arginine methyltransferase 1 (CARM1), a protein arginine N-methyltransferase (PRMT) family Enzyme, is associated with various diseases including cancers. Consequently, the development of small-molecule inhibitors targeting PRMTs has significant value for both research and therapeutic purposes. In this study, together with structure-based virtual screening with biochemical assays, two compounds DC_C11 and DC_C66 were identified as novel inhibitors of CARM1. Cellular studies revealed that the two inhibitors are cell membrane permeable and effectively blocked proliferation of Cancer cells including HELA, K562, and MCF7. We further predicted the binding mode of these inhibitors through molecular docking analysis, which indicated that the inhibitors competitively occupied the binding site of the substrate and destroyed the protein-protein interactions between CARM1 and its substrates. Overall, this study has shed light on the development of small-molecule CARM1 inhibitors with novel scaffolds.

Figures
Products