Eigenvalue analysis of peroxisome proliferator-activated receptor gamma agonists.
Eigenvalue analysis (EVA) was conducted on a series of potent agonists of peroxisome proliferator-activated receptor gamma (PPARgamma). Predictive EVA quantitative structure-activity relationship (QSAR) models were established using the SYBYL package, which had conventional r2 and cross-validated coefficient (q2) values up to 0.920 and 0.587 for the AM1 method and 0.863 and 0.586 for the PM3 method, respectively. These models were validated by a test set containing 18 compounds. The capability to predict by these two models for PPARgamma agonists, with the best predictive r2pred value of 0.614 for AM1 and 0.822 for PM3 methods, set a successful example for applying a similar approach in building QSAR models for PPARalpha and -delta that could potentially offer a new opportunity in the design of novel PPAR modulators.
Liao
Chenzhong
C
Chipscreen Biosciences, Ltd, Research Institute of Tsinghua University, Suite C301, PO Box 28, Shenzhen, Guangdong 518057, China.
Xie
Aihua
A
Shi
Leming
L
Zhou
Jiaju
J
Lu
Xianping
X
D008956:Models, Chemical; D015394:Molecular Structure; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D014157:Transcription Factors / Q000819:agonists*
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors