GDC-0879
Catalog No.S1104 Synonyms: AR-00341677
Molecular Weight(MW): 334.37
GDC-0879 is a novel, potent, and selective B-Raf inhibitor with IC50 of 0.13 nM in A375 and Colo205 cells with activity against c-Raf as well; no inhibition known to other protein kinases.
6 Customer Reviews
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Melanoma cell viability and in vivo growth by cyclindependent kinase 2/4 inhibition. Western blot analysis for c-Jun, phosphorylated-ERK1/2 (Thr202/Tyr204) (p-ERK1/2), and total ERK1/2 protein levels was done for human melanoma cell lines treated with the BRAFV600E inhibitor GDC-0879 (1 μM), or MEK inhibitors CI-1040 (1 μM), U0126 (1 μM), and PD98059 (10 μM) for 18 hours.
J Natl Cancer Inst 2012 104(21), 1673-9. GDC-0879 purchased from Selleck.
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Melanoma cell viability and in vivo growth by cyclindependent kinase 2/4 inhibition. In vivo growth of LOXIMVI xenografts in athymic nude Foxn1nu mice is shown. Tumors were allowed to grow to a maximum volume of 250mm3, and the mice were subsequently treated daily at the indicated dose levels with CDK2/4 inhibitors by intraperitoneal injection in combination with a BRAFV600E- or MEK-inhibitor. CDK2/4 inhibitor (CVT-313/indolocarbazole CDK4-I) treatment sensitizes tumors to GDC-0879 and CI1040.
J Natl Cancer Inst 2012 104(21), 1673-9. GDC-0879 purchased from Selleck.
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RAF inhibitors induce dimer formation between KSR and RAF, and activate KSR by CRAF. (A) GDC0879 but not PLX4720 induces BRAF/CRAF dimers. Cells overexpressing myc-CRAF and BRAF were treated with drug for 1 h and CRAF immunoprecipitates were immunoblotted for BRAF and CRAF (epitope tagged with myc). (B) GDC0879 but not PLX4720 enhances KSR/BRAF complexes. KSR immunoprecipitates were prepared from cells overexpressing FLAG-KSR and BRAF after treatment with the indicated drug for 1 h and immunoblotted using antibodies to BRAF. (C) Both GDC0879 and PLX4720 induce KSR/CRAF complexes.KSR immunoprecipitates were prepared from cells overexpressing FLAG-KSR and myc-CRAF after treatment with the indicated drug for 1 h and immunoblotted for CRAF using myc antibodies. (D and E) Requirement of KSR for drug-induced ERK activation. Lysates fromwild-type and KSR deficient fibroblasts, transfected with RASV12, were treated with the indicated doses of either GDC-0879 (D) or PLX4720 (E) for 1 h. Lysates were immunoblotted for phospho-ERK1 and 2, ERK2, and RASV12. (F) KSR and CRAF cooperate to activate MEK. Cells expressing the indicated constructs were treated with a 50 μM PLX4720 for 2 h before cell lysates were prepared and analyzed for pMEK by immunoblotting. CRAF(TM) refers to the T421M gatekeeper mutant that cannot bind to the drug(4). (G) KSR in vitro kinase reactions. Cells were cotransfected with WT or ATP binding deficient KSR and CRAF and immunoprecipitates prepared after cells were treated with an activating dose of PLX (10 μM) for 1 h. KSR immunoprecipitates were prepared, pretreated with 50 μM PLX4720 to inhibit coprecipitating RAF activity, and then tested for kinase activity using purified MEK. MEK phosphorylation was detected using a pMEK specific antibody.
Proc Natl Acad Sci USA 2011 108, 6067-6072. GDC-0879 purchased from Selleck.
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B-RafV600E mutated melanoma line, A375, was treated with different doses of GDC0879 for 1 h or 24 h. Cell lysates were analyzed by Western blotting to determine the levels of phosphorylated MEK1/2 (pMEK1/2) and phosphorylated ERK1/2 (pERK1/2).
Dr. Jong-in Park from Medical College of Wisconsin. GDC-0879 purchased from Selleck.
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Effect of RAF or multikinase inhibitors on RAF1-proficient and -deficient DIH. Immunoblot analysis of DIH treated with GDC-0879 (GDC), Sorafenib (SOR) or PP2. Proliferation was assessed after a 48 h treatment, and immunoblotting after 1 h treatment. TUBA, loading control.
Nat Commun, 2016, 7:13781. GDC-0879 purchased from Selleck.
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Lu1205 were treated with protein kinase inhibitors. Cell cycle protein expression was analyzed by western blot.
Med Oncol, 2017, 35(1):7. GDC-0879 purchased from Selleck.
Purity & Quality Control
Choose Selective Raf Inhibitors
Biological Activity
| Description | GDC-0879 is a novel, potent, and selective B-Raf inhibitor with IC50 of 0.13 nM in A375 and Colo205 cells with activity against c-Raf as well; no inhibition known to other protein kinases. | ||||||||||||||||||||||||||||||
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| In vitro |
GDC-0879 also inhibits cellular pERK with IC50 of 63 nM. GDC-0879 shows comparable potency in A375 melanoma and Colo205 colorectal carcinoma cell lines, both of which are B-RafV600E mutant, with IC50 of 59 nM and 29 nM for pMEK1 inhibition respectively. GDC-0879 potently inhibits B-RafV600E in Malme3M cells with IC50 of 0.75 μM. GDC-0879 also shows EC50 values < 0.5 μM in many tumor cells (A375, 624, SK-MEL-28, Malme3M, C32, 928, 888, G-361, Colo205, Colo206, SW1417, CL34, and Colo201). [1] |
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| Cell Data |
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| In vivo | In GDC-0879 treated mice, both cell line- and patient-derived BRAFV600E tumors exhibit stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared to mutant KRAS-expressing tumors. Although there is involvement of activated RAF signaling in RAS-induced tumorigenesis, decreased time to progression is observed for some KRAS-mutant tumors following GDC-0879 administration. Whereas GDC-0879-mediated efficacy is associated strictly with B-RafV600E status, MEK inhibition also attenuates proliferation and tumor growth of cell lines expressing wild-type BRAF (81% KRAS mutant, 38% KRAS wild type). The responsiveness of B-RafV600E melanoma cells to GDC-0879 could be dramatically altered by pharmacologic and genetic modulation of PI3K pathway activity. [2] |
Protocol
| Animal Research:[2] |
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Solubility (25°C)
| In vitro | DMSO | 66 mg/mL warmed (197.38 mM) |
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| Ethanol | 5 mg/mL (14.95 mM) | |
| Water | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 0.5% methylcellulose+0.2% Tween 80 For best results, use promptly after mixing. |
30 mg/mL |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 334.37 |
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| Formula | C19H18N4O2 |
| CAS No. | 905281-76-7 |
| Storage | powder |
| in solvent | |
| Synonyms | AR-00341677 |
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