Stemcell, 72982, AZ628​

AZ628 is a quinazolinone that inhibits several Rapidly accelerated fibrosarcoma (RAF) kinases, including B-RAF, B-RAF V600E, and C-RAF-1 (in vitro kinase assay IC₅₀ values of 105, 34, and 29 nM respectively; Khazak et al.). It strongly promotes B-Raf dimerization as a tight-binding inhibitor with a very slow off rate (Hatzivassiliou et al.; Lavoie et al.). From specificity profiling it is known to prevent activation of several other tyrosine kinases, including kinase insert domain receptor (KDR), discoidin domain receptor 2 (DDR2), Lck/Yes Novel (LYN), feline McDonough sarcoma (FMS), and FMS-like tyrosine kinase 1 (FLT1) (Khazak et al.).

CANCER RESEARCH

· Inhibits tumor growth, induces cell cycle arrest and causes apoptosis in a variety of cancer cell lines, especially in lines with the B-RAF V600E mutation (McDermott et al.; Khazak et al.).