Nonsteroidal progesterone receptor ligands with unprecedented receptor selectivity

The Hypolipidemic Natural Product Guggulsterone Is a Promiscuous Steroid Receptor Ligand

“…Radioligand binding assays were performed using either the charcoal separation or scintillation proximity technology as described previously (Palmer et al, 2000;Bramlett et al, 2003). Tritiated radioligands were used for all assays with the exception of thyroid hormone receptor (TR) and included dexamethasone (GR), methyltrienolone (R1881) (AR), aldosterone (MR), promegestone (R5020) (PR), GW4064 (FXR), T1317 (liver X receptor ␣, LXR␣), 9-cis retinoic acid, 17␤-estradiol (ER), peroxisome proliferator-activated receptor (PPAR) ␣ and PPAR␦ (LY427697), and PPAR␥ (LY509547) (Brooks et al, 2001;Xu et al, 2004).…”

“…Induction of alkaline phosphatase activity in the T-47D breast cancer cell line is a commonly used assay to assess the activity of compounds with PR activity (Palmer et al, 2000). Thus, we used this assay to assess the activity of both (E)-and (Z)-GS in a cell line expressing endogenous levels of PR.…”

Molecular interactions of natural and synthetic steroids in female hamsters’ flank organs

“…For competitive studies, tubes containing 0.4 nM of [ 3 H] R5020 [22]; plus a range of increasing concentrations (1 Â 10 À10 -4 Â 10 À6 M) of cold R5020 or steroids 5 and 6 (1 Â 10 À10 -4 Â 10 À6 M) in ethanol or chloroform, or in absence of the competitor were prepared, the solvent was eliminated in vacuum. We determined also the competitive binding of the antiprogestin RU486 to the PR using different concentrations of this steroid (1 Â 10 À10 -4 Â 10 À6 M) and 0.4 nM of [ 3 H] R5020.…”

Non-Steroidal Steroid Receptor Modulators

“…The oxy-bridged compound 16 showed affinity enhanced by a factor 3 on the bone PR. Since the last publication in 2000 [7] no new details on in vitro and in vivo effects have been reported.…”