GDC-0879
GDC-0879 (CAS 905281-76-7) is a selective inhibitor of B-Raf kinase, targeting the Raf/MEK/ERK signaling cascade implicated in tumorigenesis. It specifically inhibits B-Raf harboring the V600E mutation, demonstrating IC50 values of 0.13 nM against purified mutant B-Raf and 63 nM for phosphorylated ERK in MALME-3M cells. In vitro assays using V600E mutant cell lines (A375 melanoma, Colo205 colorectal cancer) illustrate the compound's selectivity towards B-Raf and related C-Raf kinases. In mouse xenografts expressing human BRAFV600E tumors, GDC-0879 treatment results in sustained (>90%) inhibition of ERK phosphorylation and reduced tumor progression, highlighting its research value in oncology studies involving Raf pathway modulation.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 334.37 |
| Cas No. | 905281-76-7 |
| Formula | C19H18N4O2 |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥16.7 mg/mL in DMSO |
| Chemical Name | 2-[4-[(1E)-1-hydroxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]ethanol |
| SDF | Download SDF |
| Canonical SMILES | C1CC(=NO)C2=C1C=C(C=C2)C3=CN(N=C3C4=CC=NC=C4)CCO |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment[1]: | |
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Cell lines |
Human melanoma A375 cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
24 h, 10 μM |
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Applications |
GDC-0879 is a potent, selective and orally bioavailable RAF small-molecule inhibitor. GDC-0879 effectively inhibited phospho-ERK with an IC50 value of 63 nmol/L and inhibited cellular viability of BRAF-mutant Malme3M cells with an EC50 value of 0.75 μmol/L. Moreover, there was a strong correlation between activating mutations of the BRAF oncogene and GDC-0879 sensitivity. |
| Animal experiment [2]: | |
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Animal models |
Tumor xenograft female athymic nu/nu mice |
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Dosage form |
Oral administration, 15, 25, 50, 100, and 200 mg/kg |
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Application |
GDC-0879 inhibited tumor growth in A375 xenograft tumor-bearing mice in a dose-dependent manner and inhibited phosphorylation of MEK1 in A375 xenografts in a concentration-dependent manner with IC50 value of 3.06 μM. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Hoeflich K P, Herter S, Tien J, et al. Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression[J]. Cancer research, 2009, 69(7): 3042-3051. [2]. Wong H, Belvin M, Herter S, 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]. Journal of Pharmacology and Experimental Therapeutics, 2009, 329(1): 360-367. |
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| Description | GDC-0879 is a novel, potent, and selective inhibitor of B-Raf with an IC50 value of 0.13 nM. | |||||
| Targets | B-Raf | c-Raf | ||||
| IC50 | 0.13 nM | |||||
Quality Control & MSDS
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Chemical structure
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