| In vitro |
AZD9496 showed pmol/L equipotent binding to both ERα and ERβ isoforms. AZD9496 directly targets ERα for downregulation in vitro. And it also antagonizes and downregulates mutant ER in vitro and in vivo. The IC50s of ERα binding, ERα downregulation, ERα antagonism for AZD9496 are 0.82, 0.14 and 0.28 nM, respectively[1].
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| In vivo |
AZD9496 showed high oral bioavailability across three species (F% 63, 91, and 74, rat, mouse, and dog, respectively) with generally low volume and clearance across species, albeit a higher clearance in mouse. The percent free levels in human plasma of 0.15% were 5-fold higher than those measured for fulvestrant. AZD9496 is a potent, oral inhibitor of breast tumor growth in vivo. AZD9496 causes tumor regressions in combination with PI3K pathway and CDK4/6 inhibitors and in an estrogen-deprived ER+ model of resistance. This effect was accompanied by a dose-dependent decrease in PR protein levels. AZD9496 is currently being evaluated in a phase I clinical trial[1].
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COA
HPLC