Journal
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
Volume 29, Issue 4, Pages 339-348Publisher
SPRINGER
DOI: 10.1007/s10822-014-9826-z
Keywords
Structure-based virtual screening; c-MYC promoter G-quadruplex; Anticancer
Categories
Funding
- Basic Science Research Program - through the National Research Foundation of Korea - Ministry of Education, Science and Technology [2010-0029358]
- Korea Healthcare technology R&D Project, Ministry for Health Welfare [A092006]
- National Research Foundation of Korea [2010-0029358, 2012R1A5A2A28671860] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
G-quadruplex DNA formed in NHEIII1 region of oncogene promoter inhibits transcription of the genes. In this study, virtual screening combining pharmacophore-based search and structure-based docking screening was conducted to discover ligands binding to G-quadruplex in promoter region of c-MYC. Several hit ligands showed the selective PCR-arresting effects for oligonucleotide containing c-MYC G-quadruplex forming sequence. Among them, three hits selectively inhibited cell proliferation and decreased c-MYC mRNA level in Ramos cells, where NHEIII1 is included in translocated c-MYC gene for overexpression. Promoter assay using two kinds of constructs with wild-type and mutant sequences showed that interaction of these ligands with the G-quadruplex resulted in turning-off of the reporter gene. In conclusion, combined virtual screening methods were successfully used for discovery of selective c-MYC promoter G-quadruplex binders with anticancer activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available