Study on the bioactivity against hematologic malignancies and theoretical binding mechanism of a novel PI3K inhibitor JN-65
10.11665/j.issn.1000-5048.20190405
- VernacularTitle:一种新型PI3K抑制剂JN-65的抗肿瘤活性及其分子模拟机制研究
- Author:
Ke KE
1
;
Wenli JIANG
;
Yu WANG
;
Jingyu ZHU
;
Jian JIN
Author Information
1. 江南大学药学院药物设计与分子药理学实验室
- Publication Type:Journal Article
- Keywords:
PI3K inhibitor;
JN-65;
hematologic malignanciesl;
leukemia;
molecular docking
- From:
Journal of China Pharmaceutical University
2019;50(4):410-416
- CountryChina
- Language:Chinese
-
Abstract:
The PI3K signaling pathway is frequently over-expressed in a variety of hematologic malignancies, so the development of PI3K inhibitors for the treatment of hematologic malignancies has broad application prospects. In this study, a novel PI3K inhibitor, JN-65, was identified through the investigation effects in the inhibition to hematologic malignancies. By MTT assays, JN-65 was found to effectively suppress the proliferation of hematologic malignancies, especially leukemia cell lines. The cell-free enzymatic studies demonstrated that JN-65 cloud inhibit PI3K and specifically inhibited PI3Kγ at low micromolar concentrations. Western blot confirmed that JN-65 could effectively inhibit the PI3K/Akt signaling pathway and the flow cytometry assays verified that JN-65 could induce the apoptosis of tumor cells through the suppression of PI3K signaling pathway. Finally, the molecular docking simulation method was used to explore the interaction between JN-65 and PI3K, and the inhibition mechanism of PI3K was revealed at the molecular level. In general, JN-65 would be a potential PI3K inhibitor for the treatment of hematologic malignancies.
