GDC-0879 is a potent and selective B-Raf inhibitor with an IC50 of 0.13 nM.
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GDC-0879 Estructura química
No. CAS : 905281-76-7
This product is a controlled substance and not for sale in your territory.
Based on 4 publication(s) in Google Scholar
GDC-0879 purchased from MedChemExpress. Usage Cited in:
Oncotarget. 2017 Nov 22;8(65):109135-109150.
[Abstract]
MCF-7 cells are pretreated with the indicated chemical inhibitors for 30min, followed by 15 min treatment with RA (20 μM) + EPA (80 μM).Cell extracts are prepared and subjected to western blotting analysis.
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BRaf c-Raf Raf
Descripciòn
GDC-0879 is a potent and selective B-Raf inhibitor with an IC50 of 0.13 nM.
IC50 & Target[1]
B-Raf
0.13 nM (IC50)
Cellular Effect
Cell Line
Type
Value
Description
References
A-375
EC50
> 500 nM
Compound: 3; GDC-0879
Cytotoxicity against human A375 cells harboring BRAF V600E mutant after 96 hrs by CellTiter-Glo assay
Cytotoxicity against human A375 cells harboring BRAF V600E mutant after 96 hrs by CellTiter-Glo assay
[PMID: 29461827]
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
GDC-0879 Related Antibodies
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Room temperature in continental US; may vary elsewhere.
Almacenamiento
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
1 year
-20°C
6 months
Solvente y solubilidad
In Vitro:
DMSO : 50 mg/mL (149.53 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.9907 mL
14.9535 mL
29.9070 mL
5 mM
0.5981 mL
2.9907 mL
5.9814 mL
10 mM
0.2991 mL
1.4953 mL
2.9907 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (7.48 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution.
If precipitation or phase separation occurs during preparation,
heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 0.5% CMC-Na/0.5% Tween-80 in Saline water
Solubility: 3.23 mg/mL (9.66 mM); Clear solution; Need ultrasonic and warming and heat to 60°C
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[1]. Hansen JD, et al. Potent and selective pyrazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4692-5.
[Content Brief]
[2]. Wong H, et al. Pharmacodynamics of 2-[4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl]ethan-1-ol (GDC-0879), a potent and selective B-Raf kinase inhibitor: understanding relationships between systemic concentrations, phosphorylated mitogen-activated protein kinase kinase 1 inhibition, and efficacy. J Pharmacol Exp Ther. 2009 Apr;329(1):360-7.
[Content Brief]
Ensayo celular
[2]
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].
MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Administraciòn de animales
[2]
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].
MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Referencias
[1]. Hansen JD, et al. Potent and selective pyrazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4692-5.
[Content Brief]
[2]. Wong H, et al. Pharmacodynamics of 2-[4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl]ethan-1-ol (GDC-0879), a potent and selective B-Raf kinase inhibitor: understanding relationships between systemic concentrations, phosphorylated mitogen-activated protein kinase kinase 1 inhibition, and efficacy. J Pharmacol Exp Ther. 2009 Apr;329(1):360-7.
[Content Brief]
[1]. Hansen JD, et al. Potent and selective pyrazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4692-5.
[2]. Wong H, et al. Pharmacodynamics of 2-[4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl]ethan-1-ol (GDC-0879), a potent and selective B-Raf kinase inhibitor: understanding relationships between systemic concentrations, phosphorylated mitogen-activated protein kinase kinase 1 inhibition, and efficacy. J Pharmacol Exp Ther. 2009 Apr;329(1):360-7.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
2.9907 mL
14.9535 mL
29.9070 mL
74.7675 mL
5 mM
0.5981 mL
2.9907 mL
5.9814 mL
14.9535 mL
10 mM
0.2991 mL
1.4953 mL
2.9907 mL
7.4767 mL
15 mM
0.1994 mL
0.9969 mL
1.9938 mL
4.9845 mL
20 mM
0.1495 mL
0.7477 mL
1.4953 mL
3.7384 mL
25 mM
0.1196 mL
0.5981 mL
1.1963 mL
2.9907 mL
30 mM
0.0997 mL
0.4984 mL
0.9969 mL
2.4922 mL
40 mM
0.0748 mL
0.3738 mL
0.7477 mL
1.8692 mL
50 mM
0.0598 mL
0.2991 mL
0.5981 mL
1.4953 mL
60 mM
0.0498 mL
0.2492 mL
0.4984 mL
1.2461 mL
80 mM
0.0374 mL
0.1869 mL
0.3738 mL
0.9346 mL
100 mM
0.0299 mL
0.1495 mL
0.2991 mL
0.7477 mL
GDC-0879 Related Classifications
MAPK/ERK Pathway
Raf
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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