Screening of small molecule inhibitors for PLK1 PBD and evaluation of antitumor activities
10.16438/j.0513-4870.2017-0028
- VernacularTitle:以PLK1 PBD为靶点小分子抑制剂的筛选及抗肿瘤活性研究
- Author:
Yu-huan JIANG
1
;
Jing ZHANG
2
;
Yun-yu CHEN
2
;
Yan-hong WANG
1
;
Shu-yi SI
2
Author Information
1. Heilongjiang University of Chinese Medicine, Haerbin 150000, China
2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
antitumor drug;
fluorescence polarization method;
PLK1 PBD inhibitor;
serine/threonine protein kinase;
polo-like kinase inhibitor
- From:
Acta Pharmaceutica Sinica
2017;52(3):409-415
- CountryChina
- Language:Chinese
-
Abstract:
With the method of fluorescence polarization (FP), we screened small molecule inhibitors for PLK1 PBD to identify the lead compounds for antitumor drugs. FP led to the identification of a potent hit, F083-0063, whose inhibition rate was (99.7±0.4)% at 10 μg·mL-1. The IC50 was calculated to be 1.9±0.1 μmol·L-1 using Graphpad Prism 5. The effect of the compound on cells' multiplication was measured by MTT assay which showed that F083-0063 inhibited the proliferation of many tumor cell lines. Flow cytometry analysis indicated that the F083-0063 promoted cell apoptosis and induced cell G2/M arrest. Migration abilities of cells, evaluated using scratch test, increased significantly in the presence of F083-0063 with the mi-gration rate as low as (37.6±0.7)% at 20 μmol·L-1. Molecular linkage technique found F083-0063 had good affinity with PLK1 PBD. The results of Western blotting showed that the expression of cyclin-dependent proteins was increased after treatment with F083-0063. In summary, F083-0063 has an antitumor activity and is expected to be an antitumor lead compound targeting PLK1 PBD.
