Tamoxifen-based probes for the study of estrogen receptor-mediated transcription.
The nuclear receptors are ideal targets to control the expression of specific genes with small molecules. Estrogen receptor can activate or repress transcription though a number of different pathways. As part of an effort to develop reagents that selectively target specific transcriptional regulatory pathways, analogs of 4-hydroxytamoxifen were synthesized with variations in the basic side chain. In vitro binding assays and cell-based luciferase reporter gene assays confirm that all the derivatives have high affinity for the receptor and high potency at repressing direct estrogen receptor-mediated transcription.
Trebley
J P
JP
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Rickert
E L
EL
Reyes
P T
PT
Weatherman
R V
RV
D000588:Amines / Q000737:chemistry; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D010597:Pharmacogenetics / Q000379:methods*; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D014158:Transcription, Genetic; D014162:Transfection
D000588:Amines; D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D008156:Luciferases