Selective Small-Chemical Inhibitors of Protein Arginine Methyltransferase 5 with Anti-Lung Cancer Activity

Collection:
Clark Atlanta University Faculty Publications
Title:
Selective Small-Chemical Inhibitors of Protein Arginine Methyltransferase 5 with Anti-Lung Cancer Activity
Creator:
Kong, Gui-Mei,
Yu, Min
Gu, Zhongping
Chen, Zhi
Xu, Rui-Ming
O'Bryant, Deon
Wang, Zhengxin
Date of Original:
2017-08-14
Subject:
African Americans--Education (Higher)--Georgia
Clark Atlanta University
Location:
United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
Medium:
articles
Type:
Text
Format:
application/pdf
Description:
Abstract: Protein arginine methyltransferase 5 (PRMT5) plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50values ranging from 0.1 to 6 ?M. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation. Oral administration of the inhibitor demonstrated antitumor activity in a lung tumor xenograft model. Thus, identified PRMT5-specific small-molecule inhibitors would help elucidate the biological roles of PRMT5 and serve as lead compounds for future drug development.
Source: PLOS One
DOI: 10.1371/journal.pone.0181601
Metadata URL:
http://hdl.handle.net/20.500.12322/cau.ir:2017_wang
Language:
eng
Original Collection:
Clark Atlanta University Faculty Publications
Holding Institution:
Clark Atlanta University
Rights:

Locations