QSAR MODELS FOR BINDING OF ESTROGENIC COMPOUNDS TO ESTROGEN-RECEPTOR ALPHA-SUBTYPE AND BETA-SUBTYPE

We have developed Quantitative Structure-Activity Relationship (QSAR) models based on Comparative Molecular Field Analysis (CoMFA) for 31 es trogenic chemicals whose relative binding affinity (RBA) is available for both ER-alpha and ER-beta. The models demonstrated a significant c orrelation (r(2)>0.95) between the CoMFA-calculated steric/electrostat ic fields and corresponding RBA data and a good predictive capability (q(2)>0.6) based on cross-validation. The CoMFA models and contour plo ts obtained for ER-alpha and ER-beta suggest a close similarity betwee n the receptors in terms of mode of binding and provide a rational bas is for ligand selectivity.