905281-76-7
905281-76-7 structure
- Name: GDC-0879
- Chemical Name: gdc-0879
- CAS Number: 905281-76-7
- Molecular Formula: C19H18N4O2
- Molecular Weight: 334.372
- Catalog: Pharmaceutical intermediate Heterocyclic compound Pyridine compound Ethylpyridine
- Create Date: 2018-12-28 05:43:39
- Modify Date: 2024-01-02 10:35:40
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GDC-0879 is a potent and selective B-Raf inhibitor with an IC50 of 0.13 nM.
| Name | gdc-0879 |
|---|---|
| Synonyms |
GDC-0879
2-{4-[(1E)-1-(Hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(4-pyridinyl)-1H-pyrazol-1-yl}ethanol 1H-Inden-1-one, 2,3-dihydro-5-[1-(2-hydroxyethyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl]-, oxime, (1E)- 2,3-Dihydro-5-[1-(2-hydroxyethyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl]-1H-inden-1-one oxime |
| Description | GDC-0879 is a potent and selective B-Raf inhibitor with an IC50 of 0.13 nM. |
|---|---|
| Related Catalog | |
| Target |
B-Raf:0.13 nM (IC50) |
| In Vitro | GDC-0879 also inhibits pERK with an IC50 of 63 nM[1]. GDC-0879 represents a novel potent and selective B-Raf inhibitor that is being evaluated as a potential antitumor agent. GDC-0879 exhibits potent inhibition of Raf/MEK/ERK signaling pathway in V600E B-Raf mutant cell lines with low cellular pMEK1 inhibition IC50 estimates of 59 and 29 nM in A375 melanoma and Colo205 colorectal carcinoma cells, respectively[2]. |
| In Vivo | The pharmacokinetic parameters of GDC-0879 after oral administration of 15, 25, 50, 100, and 200 mg/kg in MCT in mice are estimated as follows: ka=8.20 h-1, ke=0.59 h-1, and apparent volume of distribution=6.19 L/kg[2]. |
| Cell Assay | GDC-0879 in vitro IC50 estimates for pMEK inhibition are determined using A375 and Colo205 cells. In brief, A375 or Colo205 cells are incubated with a range of GDC-0879 concentrations (from 0.5 nM to 6.75 μM) for 25 min. Cells are lysed, and the lysates are subjected to centrifugation at 16,100g for 30 min, and the level of total protein is determined. Enzyme-linked immunosorbent assay kits are used to determine pMEK1 and total MEK1 protein levels in a 96-well format. Samples are analyzed in duplicate at 20 μg of protein per well. The optical densities obtained at 450 nm are converted to units per milliliter (for pMEK1) or nanograms per milliliter (for total MEK1) using a standard curve determined with recombinant pMEK1 or MEK1. The pMEK1/total MEK1 ratios are then calculated as units per nanogram. The IC50 estimates for pMEK1 inhibition are estimated by nonlinear regression using GraphPad Prism version 4.02[2]. |
| Animal Admin | Mice[2] Female athymic nu/nu mice (weighing 25-28 g) are administered oral doses of 15, 25, 50, 100, and 200 mg/kg GDC-0879. Blood samples (~1 mL) are collected at 0.5, 1, 2, 4, 8, and 24 h after dose via cardiac puncture (terminal collection) into tubes containing K2EDTA anticoagulant. Immediately upon collection, the blood is mixed with K2EDTA and stored on ice. Within 30 min, blood samples are centrifuged at approximately 1000 to 1500g for 5 min at 4°C, and plasma is harvested. The plasma samples are stored at -80°C until analysis[2]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 562.6±50.0 °C at 760 mmHg |
| Molecular Formula | C19H18N4O2 |
| Molecular Weight | 334.372 |
| Flash Point | 294.0±30.1 °C |
| Exact Mass | 334.142975 |
| PSA | 83.53000 |
| LogP | 1.12 |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.705 |
| Storage condition | -20℃ |