Definition

An orally bioavailable, second-generation inhibitor of all members of the serine/threonine protein kinase Raf family, including A-Raf, B-Raf and C-Raf protein kinases, with potential antineoplastic activity. Upon administration, pan-RAF kinase inhibitor XP-102 specifically binds to the ATP binding site of the Raf kinase positioned in the inactive DFG-out conformation, and inhibits the activity of Raf, including B-Raf mutated forms such as the B-Raf V600E mutation. This prevents the activation of Raf-mediated signal transduction pathways, which may inhibit tumor cell growth. Raf protein kinases play a key role in the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, which is often dysregulated in human cancers and plays a key role in tumor cell proliferation and survival. The valine to glutamic acid substitution at residue 600 accounts for the majority of BRAF gene mutations. The oncogenic product, BRAF(V600E) kinase, exhibits elevated activity that over-activates the MAPK signaling pathway.