Abstract
Traditional approaches to discovery of selective estrogen receptor modulators (SERMs) have relied on ER binding and cell-based estrogen response element-driven assays to identify compounds that are osteoprotective but nonproliferative in breast and uterine tissues. To discover new classes of potential SERMs, we have employed a cell-free microsphere-based binding assay to rapidly characterize ERalpha interactions with conformation-sensing cofactor or phage display peptides. Peptide profiles of constrained triarenes were compared to known proliferative and nonproliferative ER ligands to discover potent quinoline-based ligands with minimal Ishikawa cell stimulation.
MeSH terms
-
Alkaline Phosphatase / biosynthesis
-
Binding, Competitive
-
Cell Line
-
Cell Proliferation / drug effects
-
Cell-Free System
-
Endometrium / cytology
-
Enzyme Induction
-
Estrogen Receptor alpha / drug effects
-
Estrogen Receptor alpha / metabolism
-
Estrogen Receptor beta / drug effects
-
Estrogen Receptor beta / metabolism
-
Female
-
Humans
-
Ligands
-
Microspheres
-
Peptide Library
-
Quinolines / chemical synthesis*
-
Quinolines / chemistry
-
Quinolines / pharmacology
-
Receptors, Estrogen / drug effects*
-
Receptors, Estrogen / metabolism
-
Selective Estrogen Receptor Modulators / chemical synthesis*
-
Selective Estrogen Receptor Modulators / chemistry
-
Selective Estrogen Receptor Modulators / pharmacology
Substances
-
Estrogen Receptor alpha
-
Estrogen Receptor beta
-
Ligands
-
Peptide Library
-
Quinolines
-
Receptors, Estrogen
-
Selective Estrogen Receptor Modulators
-
Alkaline Phosphatase