化合物GDC-0810 T5118

Product Introduction
Bioactivity


英文名: Brilanestrant

描述: Brilanestrant (GDC-0810) 是一种雌激素选择性降能器 (selective estrogen receptor degrader)(IC50:0.7 nM)，口服具有活性。

细胞实验: 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.

动物实验: Time release pellets containing 0.72 mg 17-β estradiol are subcutaneously implanted into nu/nu mice. MCF-7 cells are grown in RPMI containing 10% FBS at 5% CO2 37°C. Trypsinized cells are pelleted and resuspended in 50% RPMI（serum free）and 50% Matrigel at 1×107 cells/mL. MCF-7 cells are subcutaneously injected (100 μL/animal) on the right flank 2-3 days post pellet implantation. Tumor volume (length × width2/2) is monitored biweekly. When tumors reach an average volume of appr 200 mm3 animals are randomized and treatment is started. Animals are treated with vehicle or compound daily for 4 weeks. Tumor volume and body weight are monitored biweekly throughout the study.

体外活性: GDC-0810 is a ERα 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]. 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].

体内活性: The pharmacokinetic profile of GDC-0810 shows it is a clearance molecule across species, with good bioavailability (40%-60%). GDC-0810 (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]. GDC-0810 exhibits low clearance (11 mL/min/kg) and 61% oral bioavailability. GDC-0810 (1-100 mg/kg/day, p.o.) displays dose-dependent efficacy in the MCF7 xenograft model [2].

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 55 mg/mL (123.07 mM)
H2O : Insoluble


关键字: inhibit | ARN810 | Estrogen Receptor/ERR | RG6046 | Inhibitor | Brilanestrant | RG-6046 | ARN 810

相关产品: Estetrol | α-Zearalenol | GSK5182 | Estradiol (cypionate) | N-Desmethyltamoxifen hydrochloride | Clomiphene citrate | ARV-471 | β-Estradiol 17-acetate | Cholesterol | Estrogen receptor modulator 10

相关库: Drug Repurposing Compound Library | Anti-Cancer Drug Library | Clinical Compound Library | Bioactive Compounds Library Max | Anti-Ovarian Cancer Compound Library | Anti-Cancer Clinical Compound Library | Anti-Cancer Active Compound Library | Target-Focused Phenotypic Screening Library | NO PAINS Compound Library | Bioactive Compound Library

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