Belvarafenib

Belvarafenib (HM95573, GDC5573) is a novel potent, selective RAF inhibitor with IC50 of 41 nM, 7 nM and 2 nM for BRAF WT, BRAF V600E and CRAF, respectively; inhibits cell proliferation of A375 (BRAF V600E) and SK-MEL-30 (NRAS Q61K) with IC50 of 57 and 24 nM, also inhibits the phosphorylations of MEK and ERK downstream kinases in mutant BRAF and mutant NRAS melanoma cells; shows the excellent antitumor activity in mouse models xenografted with both of BRAF mutation cell lines (e.g. A375 and SK-MEL-28) and NRAS mutation cell lines. (In Vitro) :Belvarafenib (Example 116) is a potent and pan RAF inhibitor with antineoplastic activity. The IC50 values of Belvarafenib are 56 nM, 7 nM and 5 nM for B-RAF, B-RAFv600E and C-RAF respectively. It also shows high inhibitory activity for FMS, DDR1 and DDR2 kinases, with IC50s of 10 nM, 23 nM and 44 nM, respectively.