Autori: Waller, Chris L.; Oprea, Tudor I.; Chae, Kun; Park, Hee-Kyoung; Korach, Kenneth S.; Laws, Susan C.; Wiese, Thomas E.; Kelce, William R.; Gray, L. Earl Jr

Editorial: Chem. Res. Toxicol., 9(8), p.1240-1248, 1996.

Rezumat:

Comparative mol. field anal. (CoMFA), a three-dimensional quant. structure-activity relation (3D-QSAR) paradigm, was used to examine the estrogen receptor (ER) binding affinities of a series of structurally diverse natural, synthetic, and environmental chems. of interest. The CoMFA/3D-QSAR model is statistically robust and internally consistent, and successfully illustrates that the overall steric and electrostatic properties of structurally diverse ligands for the estrogen receptor are both necessary and sufficient to describe the binding affinity. The ability of the model to accurately predict the ER binding affinity of an external test set of mols. suggests that structure-based 3D-QSAR models may be used to supplement the process of endocrine disrupter identification through prioritization of novel compds. for bioassay. The general application of this 3D-QSAR model within a toxicol. framework is, at present, limited only by the quantity and quality of biol. data for relevant biomarkers of toxicity and hormonal responsiveness.

Cuvinte cheie: Biological Simulation and Modeling, CoMFA, Conformation (ligand), Endocrine disruptors, Environmental estrogens, Estrogen receptor, QSAR (Structure-Activity relationships), Receptor-binding, Toxicity