ARV-471 is an orally bioavailable estrogen receptor-targeted (ER-targeted) PROTAC for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer[1].
ARV-471 induces degradation of wild-type and mutant ER (≥90%), including MCF-7 cells and ESR1 mutant lines[1]. ARV-471 can inhibit the proliferation of MCF7, T47D, T47D ER-Y537S and T47D ER-D538G cells, with GI50 of 3.3, 4.5, 7.9 and 5.7 nM, respectively[2].
ARV-471 (10 and 30 mpk, 27 days) can inhibit the growth of Patient-Derived tumor Xenograft model with ESR1 mutations and has a good tumor inhibitory effect[1]. ARV-471 (3, 10 and 30 mg/kg, 28 days) dose-dependently inhibited tumor growth in the MCF7 orthotopic xenograft model and promoted ER degradation (≥94%)[2].
References:
[1] Snyder L B, Flanagan J J, Qian Y, et al. The discovery of ARV-471, an orally bioavailable estrogen receptor degrading PROTAC for the treatment of patients with breast cancer[J]. Cancer Res, 2021, 81(13): 44.
[2] Gough S M, Flanagan J J, Teh J, et al. Oral estrogen receptor PROTAC® vepdegestrant (ARV-471) is highly efficacious as monotherapy and in combination with CDK4/6 or PI3K/mTOR pathway inhibitors in preclinical ER+ breast cancer models[J]. Clinical Cancer Research, 2024.
ARV-471 是一种口服生物可利用的雌激素受体靶向（ER靶向）PROTAC, 用于治疗局部晚期或转移性ER+/HER2-乳腺癌患者[1]。
ARV-471可诱导野生型和突变型 ER 降解 （≥90%），包括 MCF-7 细胞和 ESR1 突变系[1]。并且ARV-471可抑制 MCF7、T47D、T47D ER-Y537S 和T47D ER-D538G细胞的增殖，GI50分别为3.3、4.5、7.9和5.7nM[2]。
ARV-471（10 and 30 mpk，27 days）可以抑制ESR1 突变的人源肿瘤组织移植瘤模型中肿瘤的生长，具有良好的肿瘤抑制作用[1]。ARV-471（3、10 和 30 mg/kg, 28 days）以剂量依赖性抑制MCF7原位异种移植模型中肿瘤的生长，并且可以促进ER 的降解（≥94%）[2]。