Brilanestrant(ARN-810)是一种可口服的，选择性的雌激素降能器(selectiveestrogenreceptordegrader)，IC50值为0.7nM。
CAS：1365888-06-7
分子式：C26H20ClFN2O2
分子量：446.9
纯度：98%
存储：Store at -20°C

Background:

Brilanestrant (ARN-810) is an orally bioavailable selective estrogen receptor degrader (SERD) with IC50 of 0.7 nM.

Brilanestrant (ARN-810) is a potent ER-α binder (IC50=6.1 nM), a full transcriptional antagonist with no agonism (3× ERE, IC50=2 nM), and displays good potency and efficacy in ER-α degradation (EC50=0.7 nM) and MCF-7 breast cancer cell viability (IC50=2.5 nM) assays[1]. Brilanestrant (ARN-810) induces a distinct ERα conformation versus tamoxifen and other ER therapeutics, and does not exhibit tamoxifen-like ER agonism in MCF7 cells[2].

The pharmacokinetic profile of Brilanestrant (ARN-810) shows it is a olw clearance molecule across species, with good bioavailability (40%-60%). Brilanestrant (ARN-810) (3 mg/kg, p.o.) shows substantial tumor-growth inhibition in a tamoxifen-sensitive MCF-7 xenograft model, while at the highest dose of 100 mg/kg/day, all animals show tumor regression of more than 50% without weight loss[1]. Brilanestrant (ARN-810) exhibits low clearance (11 mL/min/kg) and 61% oral bioavailability. Brilanestrant (ARN-810) (1-100 mg/kg/day, p.o.) displays dose dependent efficacy in the MCF7 xenograft model[2].

[1]. By Lai, et al. Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts. J Med Chem. 2015 Jun 25;58(12):4888-904. [2]. Joseph JD, et al. The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer. Elife. 2016 Jul 13;5. pii: e15828. doi: 10.7554/eLife.15828