GDC0879 is highly selective, orally-bioavailable, oxime-containing pyrazole type inhibitor of B-Raf (V600E) kinase with a potency of 0.13 nM. [1] In a screening of a panel of kinases at 1 uM activity only RAF kinases were shown to have >90% inhibition, with only one additional kinase (casein kinase 1-delta) at >50% inhibition. [2] GDC0879 effectively reduces pERK levels at 63 nM and cellular viability of B-Raf mutant MALME3M cells at 0.75 uM. [2]

In A375 melanoma and Colo205 colorectal carcinoma cell lines, GDC0879 exhibits dose-depdnent pMEK1 inhibition of 59 and 29 nM, respectively. No evidence of apoptotic activation pathways in vitro was observed, suggesting that GDC0879's antitumor activity is based primarily on its effect on cell proflieration. [1] Pathway modulation in A375 tumors was shown to be significant (13% and 28% activity remaining at 1 and 4 hours, respectively) by measuring MEK1 phoshporylation of Ser217/221. Reduced levels of pMEK1 were still evident at 8h post dose (59%), but returned to baseline at 12h. Similar studies in SK23 tumors did not display such a strong PD effect.

Technical information:

Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4^oC desiccated, or store DMSO solution at -20^oC.

Reference:

Other Information:

Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.