AZD9496 is an orally available selective estrogen receptor(ERα) antagonist, with potential antineoplastic activity.

ERα:0.28 nM.

AZD9496以pmol/L的等效浓度同时结合ERα和ERβ亚型。在体外，AZD9496直接靶向ERα进行下调。同时，它还能在体外和体内拮抗并下调突变型ER。对于AZD9496，其ERα结合、ERα下调和ERα拮抗的IC50分别为0.82、0.14和0.28 nM[1]。

AZD9496在三种物种中展示出高口服生物利用度（F% 分别为63、91和74，分别对应大鼠、小鼠和狗），普遍表现出低体积与跨物种清除率，尽管小鼠的清除率较高。在人类血浆中的自由百分比为0.15%，是fulvestrant测量值的5倍。AZD9496是一种强效的口服乳腺癌生长抑制剂，能够在PI3K途径和CDK4/6抑制剂的组合以及雌激素匮乏的ER+抗性模型中引起肿瘤退化。这一效应伴随着剂量依赖性的PR蛋白水平下降。AZD9496目前正在进行一项第一阶段的临床试验[1]。

Cells were grown in steroid-free conditions in SILAC media containing 13C615N4 L-arginine to label ERα peptide as "heavy" and then switched to grow in media containing unlabeled l-arginine to label newly synthesized protein as "normal" with 0.1% DMSO, 300 nmol/L tamoxifen, 100 nmol/L AZD9496, or 100 nmol/L fulvestrant for the time indicated. (Only for Reference)