Format

Send to

Choose Destination
Database (Oxford). 2018 Jan 1;2018. doi: 10.1093/database/bay117.

GCDB: a glaucomatous chemogenomics database for in silico drug discovery.

Wei Y1, Li J2, Li B1, Ma C3, Xu X1, Wang X1, Liu A1, Du T1, Wang Z2, Hong Z4, Lin J1,2,3.

Author information

1
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, China.
2
Biodesign Center, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
3
Platform of Pharmaceutical Intelligence, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
4
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, China.

Abstract

Glaucoma is a group of neurodegenerative diseases that can cause irreversible blindness. The current medications, which mainly reduce intraocular pressure to slow the progression of disease, may have local and systemic side effects. Recently, medications with possible neuroprotective effects have attracted much attention. To assist in the identification of new glaucoma drugs, we created a glaucomatous chemogenomics database (GCDB; http://cadd.pharmacy.nankai.edu.cn/gcdb/home) in which various glaucoma-related chemogenomics data records are assembled, including 275 genes, 105 proteins, 83 approved or clinical trial drugs, 90 206 chemicals associated with 213 093 records of reported bioactivities from 22 324 corresponding bioassays and 5630 references. Moreover, an improved chemical similarity ensemble approach computational algorithm was incorporated in the GCDB to identify new targets and design new drugs. Further, we demonstrated the application of GCDB in a case study screening two chemical libraries, Maybridge and Specs, to identify interactions between small molecules and glaucoma-related proteins. Finally, six and four compounds were selected from the final hits for in vitro human glucocorticoid receptor (hGR) and adenosine A3 receptor (A3AR) inhibitory assays, respectively. Of these compounds, six were shown to have inhibitory activities against hGR, with IC50 values ranging from 2.92-28.43 μM, whereas one compoundshowed inhibitory activity against A3AR, with an IC50 of 6.15 μM. Overall, GCDB will be helpful in target identification and glaucoma chemogenomics data exchange and sharing, and facilitate drug discovery for glaucoma treatment.

PMID:
30371760
PMCID:
PMC6204718
DOI:
10.1093/database/bay117
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center