GDC-0879

• Catalog No.: S1104
• CAS Number: 905281-76-7
• M. F.: C19H18N4O2
• M. W.: 334.37182
• Storage: -20°C

SYNONYMS

• IUPAC name: 2-{4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridin-4-yl)-1H-pyrazol-1-yl}ethan-1-ol
• IUPAC Traditional name: 2-{4-[(1E)-1-(hydroxyimino)-2,3-dihydroinden-5-yl]-3-(pyridin-4-yl)pyrazol-1-yl}ethanol

DATABASE IDS

• CAS Number: 905281-76-7

PROPERTIES

• Target: B-Raf
• Salt Data: Free Base
• Solubility: DMSO
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Cancer

Biological Activity

• Description: GDC-0879 is a novel potent, selective B-Raf inhibitor for B-Raf^V600E with IC50 of 0.13 nM.
• Targets: B-Raf^V600E
• IC50: 0.13 nM ^[1]
• 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-Raf^V600E mutant, with an IC50 of 59 and 29 nM for pMEK1 inhibition respectively.^[1] GDC-0879 potently inhibits BRAFV600E enzymatic activity in Malme3M cells with an IC50 of 0.75 μM.^[1] All cells with GDC-0879 EC50 values <0.5 μm="" express="" v600e="" oncogenic="" alleles="" for="" braf="" (a375,="" 624,="" sk-mel-28,="" malme3m,="" c32,="" 928,="" 888,="" g-361,="" colo205,="" colo206,="" sw1417,="" cl34,="" and="" colo201).="">^[1]
• 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. ^[2] Whereas GDC-0879-mediated efficacy is associated strictly with BRAF^V600E 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 BRAF^V600E melanoma cells to GDC-0879 could be dramatically altered by pharmacologic and genetic modulation of phosphatidylinositol 3-kinase pathway activity. ^[2]

Protocol

• Protocol: Animal Study ^[2]
• Animal Models: Female nu/nu mice
• Formulation: 0.5% methylcellulose/0.2% Tween 80
• Doses: 100 mg/kg
• Administration: Oral gavage

References

• References: [1] Wong H, et al. J Pharmacol Exp Ther. 2009, 329(1), 360-367.
• References: [2] Hoeflich KP, et al. Cancer Res. 2009, 69(7), 3042-3051.

REFERENCES

• Wong H, et al. J Pharmacol Exp Ther. 2009, 329(1), 360-367.
• Hoeflich KP, et al. Cancer Res. 2009, 69(7), 3042-3051.