product name GDC-0879
Description: GDC-0879 is a potent, and highly selective, potent, and orally bioavailable B-Raf inhibitor with IC50 of 0.13 nM in A375 and Colo205 cells. In GDC-0879 -treated mice, both cell line- and patient-derived BRAF(V600E) tumors exhibited stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared with mutant KRAS-expressing tumors.
References: Arch Pharm Res. 2011 May;34(5):699-701.
334.37
Formula
C19H18N4O2
CAS No.
905281-76-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 66 mg/mL warming (197.4 mM)
Water: <1 mg/mL
Ethanol: 5 mg/mL (14.95 mM)
Solubility (In vivo)
0.5% methylcellulose+0.2% Tween 80: 8 mg/mL
Synonyms
AR-00341677
other peoduct :
| In Vitro |
In vitro activity: 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). Kinase Assay: Cell Assay: |
|---|---|
| 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. |
| Animal model | Female nu/nu mice |
| Formulation & Dosage | Formulated in 0.5% methylcellulose/0.2% Tween 80; 100 mg/kg; p.o. |
| References | [1] Wong H, et al. J Pharmacol Exp Ther. 2009, 329(1), 360-367. |
