A mechanism research of novel inhibitor of PAK1 inducing colorectal cancer DLD-1 apoptosis
10.11665/j.issn.1000-5048.20180214
- VernacularTitle:一种新型PAK1抑制剂诱导结直肠癌DLD-1细胞凋亡的机制研究
- Author:
Jiaqi WANG
;
Jiao CHEN
;
Xiaoyan SUN
;
Wuguang LU
;
Yang YANG
;
CAI CAI
;
Xiao-ning WANG
;
Peng CAO
- Publication Type:Journal Article
- Keywords:
CADD;
PAK1;
kinase activity;
proliferation inhibition;
pro-apoptosis
- From:
Journal of China Pharmaceutical University
2018;49(2):229-237
- CountryChina
- Language:Chinese
-
Abstract:
PAK1 plays an important role in the development of tumors. It is of great significance to screen and develop new PAK1 inhibitors as targeted drugs for cancer treatment. The traditional PAK1 inhibitor screening method has the problems of high cost and low efficiency. Computer virtual screening can reduce the cost of finding active lead compounds and improve the screening efficiency. In this study, a kind of PAK1 candidate compound was screened by computer assisted virtual screening combined with Z′lyteTM high flux kinase screen. In vitro enzyme activity screening showed that compound 18(K788)had good PAK1 inhibitory activity(inhibition rate was 42. 7%). Furtherly by MTT detection, it was found that K788 had significant PAK1 positive tumor killing activity, which was even better than the positive drug IPA-3. Flow cytometry and Western Blot showed that K788 could activate caspase apoptosis pathway and induce apoptosis of colon cancer cell DLD-1 by inhibiting PAK1 expression and activation. K788 has great potential for clinical development and application, and can be used as a PAK1 target for further research.
