1365888-06-7
1365888-06-7 structure
- Name: GDC-0810
- Chemical Name: gdc-0810
- CAS Number: 1365888-06-7
- Molecular Formula: C26H20ClFN2O2
- Molecular Weight: 446.90
- Catalog: Research Areas Cancer
- Create Date: 2017-07-23 07:56:06
- Modify Date: 2024-01-09 18:20:17
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GDC-0810 is an orally bioavailable selective estrogen receptor degrader (SERD) with IC50 of 0.7 nM.
| Name | gdc-0810 |
|---|---|
| Synonyms |
(2E)-3-{4-[(1E)-2-(2-Chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)-1-buten-1-yl]phenyl}acrylic acid
ARN-810 (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid 2-Propenoic acid, 3-[4-[(1E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)-1-buten-1-yl]phenyl]-, (2E)- |
| Description | GDC-0810 is an orally bioavailable selective estrogen receptor degrader (SERD) with IC50 of 0.7 nM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 0.7 nM (estrogen receptor) |
| In Vitro | 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[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]. |
| In Vivo | The pharmacokinetic profile of GDC-0810 shows it is a olw 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]. |
| 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) |
| Animal Admin | 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. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 622.8±55.0 °C at 760 mmHg |
| Molecular Formula | C26H20ClFN2O2 |
| Molecular Weight | 446.90 |
| Flash Point | 330.4±31.5 °C |
| PSA | 49.49000 |
| LogP | 7.82 |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.690 |
| Storage condition | -20℃ |