Brilanestrant

Brilanestrant (ARN-810; GDC-0810) is an orally bioavailable selective estrogen receptor degrader (SERD) with IC₅₀ of 0.7 nM. IC50 & Target: IC50: 0.7 nM (estrogen receptor) In Vitro: Brilanestrant (ARN-810; GDC-0810) 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; GDC-0810) induces a distinct ERα conformation versus tamoxifen and other ER therapeutics, and does not exhibit tamoxifen-like ER agonism in MCF7 cells^[2]. In Vivo: 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].