azd9496-maleate

Description: AZD9496 maleate is a novel, potent, orally bioavailable, and selective estrogen receptor (ERalpha) downregulator and antagonist with an IC50 of 0.28 nM and a Ki of 0.7 nM. AZD9496 showed pmol/L equipotent binding to both ERalpha and ERbeta isoforms. AZD9496 directly targets ERalpha for downregulation in vitro. And it also antagonizes and downregulates mutant ER in vitro and in vivo. The IC50s of ERalpha binding, ERalpha downregulation, ERalpha antagonism for AZD9496 are 0.82, 0.14 and 0.28 nM, respectively. AZD9496 bound and downregulated clinically relevant ESR1 mutants in vitro and inhibited tumor growth in an ESR1-mutant patient-derived xenograft model that included a D538G mutation. Collectively, the pharmacologic evidence showed that AZD9496 is an oral, nonsteroidal, selective estrogen receptor antagonist and downregulator in ER(+) breast cells that could provide meaningful benefit to ER(+) breast cancer patients. AZD9496 is currently being evaluated in a phase I clinical trial.

References: Cancer Res. 2016 Jun 1; 76(11):3307-18.

Related CAS#: 1639042-28-6 (maleate); 1639042-08-2 (free)