Abigail Klein – Pharmaceutical Sciences

20200408_Poster_Abigail_Spring_Research_Festival

WT-IV-12 and LY500307 Show Estrogen Receptor-β Selectivity in vitro and in vivo

“Introduction: Based on demonstrated ERβ selective transcriptional activity in a cellular model, it was hypothesized that in vivo, efficacious doses of WT-IV-12 could be determined that have only very minimal activity in ERα dependent tissues.

Methods: We used uterotrophic simulation in an estrogen naive female mouse to asses ERα activity. Briefly, groups of mice were administered escalating doses of the ERβ selective agonist WT-IV-12 in a vehicle of 5% DMSO, 5% Tween 80 in water and compared to a control ERβ selective ligand, LY500307, in a vehicle of 1% MC, 0.25% Tween 80 in water. The ERα effects of each ligand were characterized using body weight normalized uterine tissue weights.

Results: WT-IV-12 demonstrated ERβ selective activity at doses less than 30 mg/kg whereas LY500307 showed only minimal ERα effects at doses up to 100 mg/kg.

Conclusions: Consistent with cellular activity data, uterotrophic stimulation data suggests 10 mg/kg doses of WT-IV-12 demonstrating efficacy in various models of disease are ERβ selective. Our data also suggests LY500307 may be ERβ selective at doses up to 100 mg/kg.”