"It has been shown that vemurafenib binding to BRAF V600E paradoxically activates downstream MAPK signaling via dimerization with non mutant RAF family members and allosteric activation of the non mutant partner [XREF_BIBR]."
"The kinase domain of B-raf V600E has strong structural homology with the kinase domains of hRIPK1 and hRIPK3, which explains the similarities between the crystal structure of Nec-1 bound to RIPK1 and the structure of Vemurafenib bound to B-Raf V600E."
"Additionally, vemurafenib has been found to induce the trans-activation of WT-BRAF or CRAF through hetero-dimerization between vemurafenib bound BRAF V600E and WT-BRAF or CRAF."
"Based on prior structural data of MEK1-BRAF, vemurafenib bound V600E BRAF, and MEK1-KSR2 and structural alignments of vemurafenib bound V600E BRAF with BRAF or KSR2, we hypothesized a regulatory V600E BRAF- MUT MEK complex where V600E BRAF arginine 662 makes critical contacts with MEK residues in one complex interface (XREF_FIG)."
"PLX4032 binds V600E mutant BRAF with high affinity and inhibits ERK signaling output."