Definition

An orally bioavailable, small molecule inhibitor of the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutant V600E, with potential antineoplastic activity. Upon oral administration, BRAF V600E inhibitor HLX208 selectively binds to and inhibits the activity of BRAF V600E kinase, which may result in the inhibition of an over-activated MAPK signaling pathway downstream in BRAF(V600E) kinase-expressing tumor cells and a reduction in tumor cell proliferation. BRAF belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway. The valine to glutamic acid substitution at residue 600 accounts for the majority of BRAF gene mutations. The oncogenic product, BRAF(V600E) kinase, exhibits a markedly elevated activity that over-activates the MAPK signaling pathway.