A three-dimensional pharmacophore model for dipeptidyl peptidase IV inhibitors.
Dipeptidyl peptidase IV (DPP-IV) is a valid drug target for type-2 diabetes and DPP-IV inhibitors have been proven to efficiently improve glucose tolerance. In our study, 3D pharmacophore models were generated using a training set of 22 DPP-IV inhibitors. The best model consisted of important chemical features and mapped well into the active site of DPP-IV. The model gave high correlation coefficients of 0.97 and 0.84 for the training set and the test set, respectively, showing its good predictive ability for biological activity. Furthermore, the pharmacophore model demonstrated the capability to retrieve inhibitors from database with a high enrichment factor of 42.58. All results suggest that the model provides a useful tool for designing novel DPP-IV inhibitors.
Lu
I-Lin
IL
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan.
Tsai
Keng-Chang
KC
Chiang
Yi-Kun
YK
Jiaang
Weir-Torn
WT
Wu
Ssu-Hui
SH
Mahindroo
Neeraj
N
Chien
Chia-Hui
CH
Lee
Shiow-Ju
SJ
Chen
Xin
X
Chao
Yu-Sheng
YS
Wu
Su-Ying
SY
D001665:Binding Sites; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure
D054873:Dipeptidyl-Peptidase IV Inhibitors; D018819:Dipeptidyl Peptidase 4