Fig. 8: Evidence of ER agonism of AZ’6421 and compound 8 in vitro and in vivo.
From: Metabolism-driven in vitro/in vivo disconnect of an oral ERɑ VHL-PROTAC
a 100 nM compound or 10 nM estradiol (E2) were incubated with Ishikawa cells for 48 h and lysates measured for PR expression by western blot. b Normalised rat uterine weight shown as % change from respective vehicle control after 4 days dosing. c Representative H&E stained images taken from sections of uterine horn after 4 days of dosing. d Total plasma exposure of AZ’6421 and its metabolite 8 following dosing of 100 mg/kg BID or 30 mg/kg BID AZ’6421. Plasma samples were taken 4 hr after the 4th dose, at the same time as the uterus was weighed and sectioned for H&E staining.
