GDC-0879

SKU: orb1300873

Description

GDC-0879 is a potent and selective small molecule inhibitor of B-Raf (IC50 = 0.13 nM) with additional activity against c-Raf. It is a valuable research tool for investigating MAPK/ERK pathway signaling in cancer biology, utilized in both in vitro cellular assays and in vivo xenograft models to study oncogenic BRAF-driven proliferation.

Research Area

Signal Transduction

Key Properties

• CAS Number: 905281-76-7
• MW: 334.37
• Purity: 99.93% (May vary between batches)
• Formula: C₁₉H₁₈N₄O₂
• SMILES: OCCn1cc(c(n1)-c1ccncc1)-c1ccc2\C(CCc2c1)=N\O
• Target: Raf
• Solubility: DMSO:150 mg/mL (448.6 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.98 mM)

Bioactivity

• Target IC50:
  B-Raf:0.13 nM
• 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.
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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).
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Raf, Raf kinases, inhibit, Inhibitor, GDC0879, GDC-0879, GDC 0879, AR 00341677, AR00341677, AR-00341677, B-Raf

Compound Identifiers

PubChem CID

11717001