In vitro activity: Brilanestrant (formerly known as GDC-0810, ARN-810 and/or RG6046) is a potent and orally bioavailable Selective Estrogen Receptor Degrader (SERD) that demonstrates robust activity in models of tamoxifen-sensitive and tamoxifen-resistant breast cancer, and is currently in clinical trials in women with locally advanced or metastatic estrogen receptor-positive breast cancer.tamoxifen-resistant breast cancer xenografts. GDC-0810 induces a distinct ERα conformation versus tamoxifen and other ER therapeutics, and does not exhibit tamoxifen-like ER agonism in MCF7 cells.

Kinase Assay: 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.

Cell Assay: MCF-7 cells are adjusted to a concentration of 40000 cells per mL in RPMI containing 10% FBS and 20 mM HEPES. Then 16 μL of the cell suspension (640 cells) is added to each well of a 384-well plate, and the cells are incubated overnight to allow the cells to adhere. The following day a 10-point, serial 1:5 dilution of each compound is added to the cells in 16 μL at a final concentration ranging from 10 to 0.000005 μM. After 5 days' compound exposure, 16 μL of CellTiter-GLo is added to the cells, and the relative luminescence units of each well are determined. CellTiter-GLo added to 32 μL of medium without cells is used to obtain a background value. The percent viability of each sample is determined as follows: (RLU sample-RLU background/RLU untreated cells-RLU background ×100=%viability).