Pharmacophore modeling, virtual screening, and molecular docking studies for discovery of novel Akt2 inhibitors.
Akt2 is considered as a potential target for cancer therapy. In order to find novel Akt2 inhibitors which have different scaffolds, structure-based pharmacophore model and 3D-QSAR pharmacophore model were built and validated by different methods. Then, they were used for chemical databases virtual screening. The selected compounds were further analyzed and refined using drug-like filters and ADMET analysis. Finally, seven hits with different scaffolds were picked out for docking studies. These seven hits were predicted to have high inhibitory activity and good ADMET properties, they may act as novel leads for Akt2 inhibitors designing.
College of Chemical Engineering, Sichuan University, Sichuan, Chengdu, 610065, China.
Jia
J
Fei
Lu
L
Zhou
Tao
T
Liu
Xiang-Yang
XY
Tang
D062126:Databases, Chemical; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000627:therapeutic use; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship
C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt
Akt2; docking; inhibitor; pharmacophore; virtual screening.