| 货号 (SKU) | 包装规格 | 是否现货 | 价格 | 数量 |
|---|---|---|---|---|
| B421391-1ml |
1ml |
现货  |
|
| 别名 | 布林司他定 (GDC-0810) |
|---|---|
| 英文别名 | BCP24812 | Q27272746 | 1.1'carbonyldiimidazole | CCG-269201 | (E)-3-[4-[(E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-enyl]phenyl]prop-2-enoic acid | Z2634828503 | (2E)-3-{4-[(1E)-2-(2-CHLORO-4-FLUOROPHENYL)-1-(1H-INDAZOL-5-YL)BUT-1-EN-1-YL]PHE |
| 规格或纯度 | 10mM in DMSO |
| 英文名称 | Brilanestrant (GDC-0810) |
| 生化机理 | 布利奈司特（GDC-0810，ARN-810）是一种强效的 ER-α 粘合剂（ER-α，IC50 = 6.1 nM；ER-β，IC50 = 8.8 nM），是一种完全的转录拮抗剂，没有激动作用，在 ER-α 降解（EC50 = 0.7 nM）和 MCF-7 乳腺癌细胞活力（IC50 = 2.5 nM）试验中显示出良好的效力和功效，对其他核激素受体具有良好的选择性。 |
| 储存温度 | -80℃储存 |
| 运输条件 | 超低温冰袋运输 |
| 作用类型 | 拮抗剂 |
| 作用机制 | 雌激素受体α拮抗剂 |
| 产品介绍 |
Information Brilanestrant (GDC-0810, ARN-810） is a potentER-αbinder (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 (Cell-free); ERβ (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. 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. Cell Research(from reference) Cell lines：MCF-7 cells Incubation Time：4 h |
| IC50 | ERβ, IC50: 8.8 nM; ERα, IC50: 6.1 nM |
|---|---|
| ALogP | 6.808 |
| hba_count | 2 |
| HBD Count | 1 |
| Rotatable Bond | 6 |
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| 作用机制 | Action Type | target ID | Target Name | Target Type | Target Organism | Binding Site Name | 参考文献 |
|---|
| 分子类型 | 小分子 |
|---|---|
| IUPAC Name | (E)-3-[4-[(E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-enyl]phenyl]prop-2-enoic acid |
| INCHI | InChI=1S/C26H20ClFN2O2/c1-2-21(22-10-9-20(28)14-23(22)27)26(18-8-11-24-19(13-18)15-29-30-24)17-6-3-16(4-7-17)5-12-25(31)32/h3-15H,2H2,1H3,(H,29,30)(H,31,32)/b12-5+,26-21+ |
| InChi Key | BURHGPHDEVGCEZ-KJGLQBJMSA-N |
| Canonical 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 |
| Isomeric SMILES | CC/C(=C(/C1=CC=C(C=C1)/C=C/C(=O)O)\C2=CC3=C(C=C2)NN=C3)/C4=C(C=C(C=C4)F)Cl |
| 分子量 | 446.9 |
| Reaxy-Rn | 28709093 |
| Reaxys-RN link address | https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=28709093&ln= |
| DMSO(mg / mL) Max Solubility | 89 |
|---|---|
| DMSO(mM) Max Solubility | 199.1496979 |
| Water(mg / mL) Max Solubility | ＜1 |
| 分子量 | 446.900 g/mol |
| XLogP3 | 7.400 |
| 氢键供体数Hydrogen Bond Donor Count | 2 |
| 氢键受体数Hydrogen Bond Acceptor Count | 4 |
| 可旋转键计数Rotatable Bond Count | 6 |
| 精确质量Exact Mass | 446.12 Da |
| 单同位素质量Monoisotopic Mass | 446.12 Da |
| 拓扑极表面积Topological Polar Surface Area | 66.000 Ų |
| 重原子数Heavy Atom Count | 32 |
| 形式电荷Formal Charge | 0 |
| 复杂度Complexity | 719.000 |
| 同位素原子数Isotope Atom Count | 0 |
| 定义的原子立体中心计数Defined Atom Stereocenter Count | 0 |
| 未定义的原子立体中心计数Undefined Atom Stereocenter Count | 0 |
| 定义的键立体中心计数Defined Bond Stereocenter Count | 2 |
| 未定义的键立体中心计数Undefined Bond Stereocenter Count | 0 |
| 所有立体化学键的总数The total count of all stereochemical bonds | 2 |
| 共价键合单元计数Covalently-Bonded Unit Count | 1 |
| Reaxy-Rn | 28709093 |
|---|---|
| Reaxys-RN link address | https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=28709093&ln= |
| Concentration(Compounding value) | 9.0-11.0(mmol/L) |
|---|---|
| Appearance(Colorless Transparent Liquid) | Pass |
| Record the entire process by video | Conform |
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