Reporter Gene Transactivation Assays

The compound class was further optimized towards antagonistic activity. A ring contraction to the pyrazoline scaffold and decoration of this ring with several substituents resulted in a series of compounds exemplified by 23. This displayed weak antagonistic activity in the MMTV reporter gene transactivation assay in CV-1 cells compared to mifepristone (RU-486) (Scheme 6.11). 

At least two other chemotypes, tetrahydroquinolines (Fig. 25.1.5, 25 [87-88]) and amidoketones (Fig. 25.1.5, 26 [89, 90] also reviewed in Ref. [6]) have been shown to directly (ligand binding assays) or indirectly (cell based reporter gene transactivation assays) interact with the ecdysone receptor. These new ecdysone receptor binding chemistries could lead to new products for control of insect pests not controlled by current BAH insecticides. 

Transactivation assays in stably transfected cell lines involve cells stably transfected with both human ER and ER-responsive reporter genes, the latter of which have easily detected activity [30]. Transiently transfected cells have been used successfully... 

---