2D QSAR studies on thyroid hormone receptor ligands.
2D QSAR studies were carried out for a series of 55 ligands for the Thyroid receptors, TRalpha and TRbeta. Significant cross-validated correlation coefficients (q(2)=0.781 (TRalpha) and 0.693 (TRbeta)) were obtained. The models' predictive abilities were proved more valuable than the classical 2D-QSAR, and were further investigated by means of an external test set of 13 compounds. The predicted values are in good agreement with experimental values, suggesting that the models could be useful in the design of novel, more potent TR ligands. Contribution map analysis identified a number of positions that are promising for the development of receptor isoform specific ligands.
Valadares
Napoleão F
NF
Departamento de Física e Informática, Instituto de Física de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense 400, 13560-970 São Carlos-SP, Brazil. napo@if.sc.usp.br
Castilho
Marcelo S
MS
Polikarpov
Igor
I
Garratt
Richard C
RC
D001185:Artificial Intelligence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D011988:Receptors, Thyroid Hormone / Q000187:drug effects*; D012984:Software; D037021:Thyroid Hormone Receptors alpha / Q000187:drug effects; D037042:Thyroid Hormone Receptors beta / Q000187:drug effects
D008024:Ligands; D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta