| Size | Price | Stock | Qty |
|---|---|---|---|
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
GDC-0879 (AR-00341677; GDC-0879; AR00341677) is a novel, potent, highly selective, and orally bioavailable B-Raf kinase inhibitor with potential antitumor activity. In A375 and Colo205 cells, it inhibits B-Raf kinase with an IC50 value of 0.13 nM. When compared to tumors derived from mutant KRAS-expressing mice, both cell line- and patient-derived BRAF(V600E) tumors showed stronger and longer-lasting pharmacodynamic inhibition (>90% for 8 hours). Cellular responses relevant to tumorigenesis, such as cell proliferation, invasion, survival, and angiogenesis, involve the Raf/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase signaling pathway.
| Targets |
B-Raf (IC50 = 0.13 nM)
|
|---|---|
| ln Vitro |
GDC-0879 also has an IC50 of 63 nM for inhibiting cellular pERK. GDC-0879 exhibits comparable potency in B-RafV600E mutant A375 melanoma and Colo205 colorectal carcinoma cell lines, with IC50 values for pMEK1 inhibition of 59 nM and 29 nM, respectively. With an IC50 of 0.75 μM , GDC-0879 potently inhibits B-RafV600E in Malme3M cells. Many tumor cells, including A375, 624, SK-MEL-28, Malme3M, C32, 928, 888, G-361, Colo205, Colo206, SW1417, CL34, and Colo201, exhibit EC50 values for GDC-0879 that are less than 0.5 μM.[1]
|
| ln Vivo |
Compared to mutant KRAS-expressing tumors, GDC-0879-treated mice with BRAFV600E tumors from both cell lines and patients show a stronger and longer-lasting pharmacodynamic inhibition (>90% for 8 hours). A decreased time to progression is seen for some KRAS-mutant tumors after GDC-0879 administration, despite the fact that activated RAF signaling is involved in RAS-induced tumorigenesis. Mek inhibition also inhibits proliferation and tumor growth in cell lines expressing wild-type BRAF (81% KRAS mutant, 38% KRAS wild type), in contrast to GDC-0879, whose efficacy is solely dependent on B-RafV600E status. Pharmacological and genetic modifications of the PI3K pathway activity may significantly alter the B-RafV600E melanoma cells' response to GDC-0879.[2]
|
| Enzyme Assay |
GDC-0879 is a potent and selective B-Raf inhibitor with an IC50 of 0.13 nM.
|
| Cell Assay |
GDC-0879 in vitro IC50 estimates for pMEK inhibition are determined using A375 and Colo205 cells. Briefly, GDC-0879 is incubated with A375 or Colo205 cells for 25 min at a range of concentrations (from 0.5 nM to 6.75 μM). Cells are lysed, and the lysates are centrifuged at 16,100 g for 30 min to determine the level of total protein. In a 96-well format, the levels of pMEK1 and total MEK1 protein are determined using enzyme-linked immunosorbent assay kits. At 20 μg of protein per well, samples are examined in duplicate. When converting optical densities obtained at 450 nm to units per milliliter (for pMEK1) or nanograms per milliliter (for total MEK1), a standard curve created using recombinant pMEK1 or MEK1 is used as a reference. Once converted to units per nanogram, the pMEK1/total MEK1 ratios are calculated. GraphPad Prism version 4.02 is used to estimate the IC50 values for pMEK1 inhibition through nonlinear regression.
|
| Animal Protocol |
Mice: GDC-0879 is given orally in doses of 15, 25, 50, 100, and 200 mg/kg to female athymic nu/nu mice (weighing 25–28 g). Through cardiac puncture (terminal collection), blood samples (~1 mL) are taken at intervals of 0.5, 1, 2, 4, 8, and 24 hours following the dose and placed into tubes containing K2EDTA anticoagulant. The blood is combined with K2EDTA as soon as it is drawn, then chilled. Within 30 minutes, plasma is extracted from blood samples that have been centrifuged at a speed of 1000 to 1500g for five minutes at 4°C. When not in use, the plasma samples are kept at -80°C.
|
| References |
|
| Additional Infomation |
GDC-0879 is a member of the class of pyrazoles that is 1-(2-hydroxyethyl)pyrazole carrying additional 4-pyridyl and 1-(hydroxyimino)indan-5-yl substituents at positions 3 and 4 respectively. It has a role as a B-Raf inhibitor and an antineoplastic agent. It is a member of pyrazoles, a member of pyridines, a member of indanes, a ketoxime and a primary alcohol.
|
| Molecular Formula |
C19H18N4O2
|
|
|---|---|---|
| Molecular Weight |
334.37
|
|
| Exact Mass |
334.142
|
|
| Elemental Analysis |
C, 68.25; H, 5.43; N, 16.76; O, 9.57
|
|
| CAS # |
905281-76-7
|
|
| Related CAS # |
|
|
| PubChem CID |
11717001
|
|
| Appearance |
Light yellow to light brown solid powder
|
|
| Density |
1.4±0.1 g/cm3
|
|
| Boiling Point |
562.6±50.0 °C at 760 mmHg
|
|
| Flash Point |
294.0±30.1 °C
|
|
| Vapour Pressure |
0.0±1.6 mmHg at 25°C
|
|
| Index of Refraction |
1.705
|
|
| LogP |
1.12
|
|
| Hydrogen Bond Donor Count |
2
|
|
| Hydrogen Bond Acceptor Count |
5
|
|
| Rotatable Bond Count |
4
|
|
| Heavy Atom Count |
25
|
|
| Complexity |
480
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
ON=C1CCC2C1=CC=C(C1C(C3C=CN=CC=3)=NN(CCO)C=1)C=2
|
|
| InChi Key |
DEZZLWQELQORIU-RELWKKBWSA-N
|
|
| InChi Code |
InChI=1S/C19H18N4O2/c24-10-9-23-12-17(19(21-23)13-5-7-20-8-6-13)15-1-3-16-14(11-15)2-4-18(16)22-25/h1,3,5-8,11-12,24-25H,2,4,9-10H2/b22-18+
|
|
| Chemical Name |
2-[4-[(1E)-1-hydroxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]ethanol
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 0.5% methylcellulose+0.2% Tween 80: 8 mg/mL Solubility in Formulation 4: 3.23 mg/mL (9.66 mM) in 0.5% CMC-Na 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
GDC-0879 is a potent and selective RAF kinase inhibitor. Cancer Res. 2009 Apr 1;69(7):3042-51. |
BRAFV600E mutation predicts for enhanced sensitivity of melanoma, colon, and lung cancer cell lines to RAF inhibitors in vitro. |
Wild-type BRAF melanoma tumors have an attenuated pharmacodynamic response to GDC-0879 treatment relative to BRAFV600E tumor xenografts. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
