Identifying Activity Cliff Generators of PPAR Ligands Using SAS Maps
Por:
Méndez-Lucio O., Pérez-Villanueva J., Castillo R., Medina-Franco J.L.
Publicada:
1 dic 2012
Resumen:
Structure-activity relationships (SAR) of compound databases play a key role in hit identification and lead optimization. In particular, activity cliffs, defined as a pair of structurally similar molecules that present large changes in potency, provide valuable SAR information. Herein, we introduce the concept of activity cliff generator, defined as a molecular structure that has a high probability to form activity cliffs with molecules tested in the same biological assay. To illustrate this concept, we discuss a case study where Structure-Activity Similarity maps were used to systematically identify and analyze activity cliff generators present in a dataset of 168 compounds tested against three peroxisome-proliferator-activated receptor (PPAR) subtypes. Single-target and dual-target activity cliff generators for PPARa and d were identified. In addition, docking calculations of compounds that were classified as cliff generators helped to suggest a hot spot in the target protein respons
Filiaciones:
Méndez-Lucio O.:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico
Pérez-Villanueva J.:
Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, UAM-X, México, DF 04960, Mexico
Castillo R.:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico
Medina-Franco J.L.:
Torrey Pines Institute of Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, United States
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