Pharmacophore modeling and virtual screening for designing potential PLK1 inhibitors.
Pharmacophore models of Polo-like kinase-1 (PLK1) inhibitors have been established by using the HipHop and HypoGen algorithms implemented in the Catalyst software package. The best quantitative pharmacophore model, Hypo1, which has the highest correlation coefficient (0.9895), consists of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic feature, and one hydrophobic aliphatic feature. Hypo1 was further validated by test set and cross validation method. Then Hypo1 was used as a 3D query to screen several databases including Specs, NCI, Maybridge, and Chinese Nature Product Database (CNPD). The hit compounds were subsequently subjected to filtering by Lipinski's rule of five and docking study to refine the retrieved hits and as a result to reduce the rate of false positive. Finally, a total of 20 compounds were selected and have been shifted to in vitro and in vivo studies. As far as we know, this is the first report on the pharmacophore modeling even the first publicly reported virtual screening study of PLK1 inhibitors.
Wang
Hui-Yuan
HY
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Chengdu, Sichuan 610041, China.
Cao
Zhi-Xing
ZX
Li
Lin-Li
LL
Jiang
Pei-Du
PD
Zhao
Ying-Lan
YL
Luo
Shi-Dong
SD
Yang
Li
L
Wei
Yu-Quan
YQ
Yang
Sheng-Yong
SY