For research use only.
Catalog No.S7855 Synonyms: ARN-810
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.
Selleck's Brilanestrant (GDC-0810) has been cited by 2 publications
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|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.|
In cell-free radio-ligand competitive binding assays, GDC-0810 binds both ERα and ERβ with low nanomolar affinity. 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). 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.
|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. GDC-0810 displays mild estrogenic activity in uterine models in vitro and in vivo.|
|In vitro||DMSO||89 mg/mL (199.14 mM)|
|Ethanol||89 mg/mL (199.14 mM)|
* 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.
In vivo Formulation Calculator (Clear solution)
|Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)|
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|% DMSO % % Tween 80 % ddH2O|
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH2O，mix and clarify.
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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|
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.
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