AZ-628 is a new pan-Raf inhibitor for BRAF, BRAFV600E, and c-Raf-1 with IC50 of 105 nM, 34 nM and 29 nM in cell-free assays. Specificity profliling indicates that AZ-628 also inhibits activation of number of tyrosine protein kinases including VEGFR2, DDR2, Lyn, Flt1, FMS and others. AZ-628 inhibits anchorage-dependent and -independent growth, causes cell cycle arrest, and induces apoptosis in colon and melanoma cell lines harboring B-RafV600E mutation. The profile of AZ-628 cross-reactivity suggests that similar to sorafenib, AZ-628 may be antiangiogenic based on inhibition of VEGFR2. AZ-628 is remarkably effective at inhibiting the growth of a specific subset of human cancer cell lines derived from melanomas, thyroid cancers, and colorectal cancers that harbor the BRAF V600E mutation. Preclinical evaluation is in progress.