NCIt definition : An orally available small-molecule inhibitor of mutant (V600E) v-raf murine sarcoma
viral oncogene homolog B1 (BRAF) with potential antineoplastic activity. BRAF(V600E)
kinase inhibitor RO5212054 selectively binds to the ATP-binding site of BRAF(V600E)
kinase and inhibits its activity, which may result in an inhibition of an over-activated
MAPK signaling pathway downstream in BRAF(V600E) kinase-expressing tumor cells and
a reduction in tumor cell proliferation. The valine to glutamic acid substitution
at residue 600 accounts for about 90% of BRAF gene mutations; the oncogenic product,
BRAF(V600E) kinase, exhibits a markedly elevated activity that over-activates the
MAPK signaling pathway. The BRAF(V600E) mutation has been found to occur in approximately
60% of melanomas, and in about 8% of all solid tumors.;