High-throughput screening for hamster chymase 2 inhibitors.
- Author:
Shou-Bao WANG
1
;
Xiao-Ming ZHU
;
Feng GAO
;
Xiao-Bin PANG
;
Guan-Hua DU
Author Information
1. National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Chymases;
analysis;
antagonists & inhibitors;
Cricetinae;
Enzyme Inhibitors;
analysis;
pharmacology;
Escherichia coli;
metabolism;
High-Throughput Screening Assays;
methods;
Inhibitory Concentration 50;
Rats;
Structure-Activity Relationship
- From:
Acta Pharmaceutica Sinica
2012;47(2):168-173
- CountryChina
- Language:Chinese
-
Abstract:
To screen potential hamster chymase 2 inhibitors, a high-throughput screening (HTS) model was established. Recombinant hamster chymase 2 with active form was cloned and expressed in E. coli. The HTS model with total volume of 50 microL in 384-well microplate was based on fluorescence analysis and was proved sensitive as well as specific (Z' = 0.84). A total of 40 080 samples (including 28 060 compounds and 12 020 natural products) were screened, and 613 samples with inhibition greater than 90% were selected for further rescreening. Finally, compounds J16647 and J16648 were identified with high inhibitory activity on chymase 2, and whose IC50 values were 0.823 and 0.690 micromol x L(-1), respectively.
