Brilanestrant (GDC-0810)

For research use only.

Catalog No.S7855 Synonyms: ARN-810

2 publications

Brilanestrant (GDC-0810) Chemical Structure

Molecular Weight(MW): 446.90

Brilanestrant (GDC-0810, ARN-810) is a potent ER-α binder (ER-α, IC50 = 6.1 nM; ER-β, IC50 = 8.8 nM), a full transcriptional antagonist with no agonism 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 with good selectivity over other nuclear hormone receptors.

Size Price Stock Quantity  
USD 147 In stock
USD 447 In stock
Bulk Discount

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

Purity & Quality Control

Choose Selective Estrogen/progestogen Receptor Inhibitors

Biological Activity

Description Brilanestrant (GDC-0810, ARN-810) is a potent ER-α binder (ER-α, IC50 = 6.1 nM; ER-β, IC50 = 8.8 nM), a full transcriptional antagonist with no agonism 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 with good selectivity over other nuclear hormone receptors.
Targets
ERα [1]
(Cell-free)
ERβ [1]
(Cell-free)
6.1 nM 8.8 nM
In vitro

In cell-free radio-ligand competitive binding assays, GDC-0810 binds both ERα and ERβ with low nanomolar affinity[2]. GDC-0810 has little to no inhibition against CYP1A2, CYP2D6, or CYP3A4 (IC50 > 20 μM), modest inhibitory effect on CYP2C9 and CYP2C19 (IC50 = 2.2 and 3.3 μM respectively), and potent inhibition of CYP2C8 (IC50 of <0.1 μM). Selectivity of GDC-0810 over other nuclear hormone receptors is also found to be good. In transcriptional reporter assays for the mineralocorticoid (MR), progesterone-A (PR-A), progesterone (PR-B), and glucocorticoid (GR) receptors, GDC-0810 has minimal activity (IC50 > 1 μM). While in binding assays, GDC-0810 displays little activity toward the androgen receptor (AR; IC50 > 4 μM) and GR (IC50 = 0.99 μM)[1]. GDC-0810-mediated ERα depletion is dependent on the 26S proteasome. GDC-0810 antagonizes ERα ligand binding domain mutants in vitro and in vivo. In cell-free E2 competitive binding assays that was used to determine the binding of GDC-0810 to ER.WT, ER.Y537S and ER.D538G ligand binding domains, GDC-0810 retains its ability to potently displace E2 from the ligand binding domain, albeit with a slightly increased IC50 (WT: 2.6 nM vs. ER.Y537S: 5.5 nM and ER.D538G: 5.4 nM). GDC-0810 can compete the PGC1α co-activator peptide off the mutated ligand binding domain, implying that GDC-0810 is capable of driving an 'active' to 'inactive' conformational shift of mutant ER, though with a ~five-seven fold reduction in biochemical potency compared to wild-type ER[2].

In vivo The pharmacokinetic profile of GDC-0810 shows it is a low clearance molecule across species, with good bioavailability (40−60%). As would be expected for a lipophilic carboxylic acid, the compound is highly bound to plasma proteins (>99.5% across species) and has a low to moderate volume of distribution (Vss = 0.2−2.0 L/kg across species). GDC-0810 exhibits good bioavailability across species and displays robust activity in tamoxifen-sensitive and tamoxifen-resistant xenograft models of breast cancer[1]. GDC-0810 displays mild estrogenic activity in uterine models in vitro and in vivo[2].

Protocol

Cell Research:

[1]

- Collapse
  • Cell lines: MCF-7 cells
  • Concentrations: --
  • Incubation Time: 4 h
  • Method:

    MCF-7 cells are trypsinized and washed twice in phenol red free RPMI containing 5% charcoal dextran stripped FBS with 20 mM HEPES and NEAA and adjusted to a concentration of 200000 cells per mL with the same medium. Next, 16 μL of the cell suspension (3200 cells) is added to each well of a poly-D-lysine coated 384-well plate, and the cells are incubated at 37℃ over 4 days to allow the cells to adhere and grow. On day 4, a 10-point, serial 1:5 dilution of each compound is added to the cells in 16 μL at a final concentration ranging from 10−5 M to 5.12 × 10−12 M or 10−6 M to 5.12 × 10−13 M for fulvestrant. At 4 h post compound addition, the cells are fixed by adding 16 μL of 30% formalin to the 32 μL of cells and compound (10% formalin final concentration) for 20 min. Cells are then washed twice with PBS Tween 0.1% and then permeabilized in PBS 0.1% Triton (50 μL/well) for additional 15 min. The PBS 0.1% triton is decanted, and the cells are washed: LI-COR blocking buffer (50 μL/well) was added, the plate is spun at 3000 rpm, and then the blocking buffer is decanted. Additional LI-COR blocking buffer (50 μL/well) is added, and the cells are incubated overnight at 4℃. The blocking buffer is decanted, and the cells are incubated overnight at 4℃ with SP1 anti-ER rabbit monoclonal antibody diluted 1:1000 in LI-COR blocking buffer/0.1% Tween-20. Wells, which are treated with blocking buffer with Tween but no antibody, are used as a background control. Wells are washed twice with PBS Tween 0.1% to remove free SP1 antibodies, and the cells are incubated at room temp for 60−90 min in LI-COR goat antirabbit IRDyeTM 800CW (1:1000) and DRAQ5 DNA dye diluted in LI-COR blocking buffer containing 0.1% Tween-20 and 0.01% SDS. Cells are then washed with 0.1%Tween-20/PBS three times. Plates are scanned on a LI-COR Odyssey infrared imaging system.


    (Only for Reference)
Animal Research:

[1]

- Collapse
  • Animal Models: a tamoxifen-sensitive MCF-7 xenograft model
  • Dosages: 30 and 100 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 89 mg/mL (199.14 mM)
Ethanol 89 mg/mL (199.14 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 446.90
Formula

C26H20ClFN2O2

CAS No. 1365888-06-7
Storage powder
in solvent
Synonyms ARN-810
Smiles CCC(=C(C1=CC=C(C=C1)C=CC(=O)O)C2=CC3=C(C=C2)NN=C3)C4=C(C=C(C=C4)F)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02802670 Completed Drug: [14C]-GDC-0810 Healthy Volunteers Genentech Inc. May 2016 Phase 1
NCT02621957 Completed Drug: GDC-0810|Drug: Pravastatin Breast Cancer Genentech Inc. December 2015 Phase 1
NCT02569801 Terminated Drug: Fulvestrant|Drug: GDC-0810 Breast Cancer Genentech Inc. December 4 2015 Phase 2
NCT01823835 Terminated Drug: GDC-0810|Drug: LHRH Agonist|Drug: Palbociclib Breast Cancer Genentech Inc. December 29 2014 Phase 1|Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

Estrogen/progestogen Receptor Signaling Pathway Map

Related Estrogen/progestogen Receptor Products

Tags: buy Brilanestrant (GDC-0810) | Brilanestrant (GDC-0810) supplier | purchase Brilanestrant (GDC-0810) | Brilanestrant (GDC-0810) cost | Brilanestrant (GDC-0810) manufacturer | order Brilanestrant (GDC-0810) | Brilanestrant (GDC-0810) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID