ERa-selective ligands

Two other novel approaches have recently been reported in the field of ER ligand discovery. The potential of compounds as pathway-selective ligands and antiinflammatory agents was studied by the use of NFKB-driven reporter assays [64], A second relatively recent focus for ER-directed drug discovery is related to the fact that there are two subtypes of this receptor, ERa and ER 1, which derive from two separate genes [65, 66], Stimulated by the specific tissue distribution pattern of these two related receptors, research to find ER subtype-selective modulators for the treatment... 

DaSilva, C.A., Pai, L.Y. et al. (2007) Estrogen receptor ligands. Part 16 2-aryl indoles as highly subtype selective ligands for ERa. Bioorganic el Medicinal Chemistry Letters, 17, 2322-2328. 

Renaud, J., Bischoff S.F., Buhl, T., Floersheim, P., Fournier, B., Halleux, C., Kallen, J., Keller, H. et al. (2003) Estrogen receptor modulators identification and structure-activity relationships of potent ERa-selective tetrahydroisoquinoline ligands. Journal of Medicinal Chemistry, 46, 2945-2957. 

Phenantrenes SignalGene reported on phenantrenes as SERM-type ligands for the ERs [180]. Most of the phenantrenes disclosed showed very low affinity for either ER, but dihydrophenantrene analog 143 showed reasonable ERa affinity (K, = 9 nM) and 22-fold ERa selectivity. 

---