In 2007, Charles Hong, M.D., Ph.D., and co-workers described using seafood embryos to display screen for compounds that interfere with signaling pathways involved in early development – pathways recognized to play roles in a variety of disease procedures. They discovered the substance ‘dorsomorphin’ and demonstrated that it blocked BMP signaling, which includes been implicated in anemia, inflammatory responses and bone-related disorders. But in examining dorsomorphin additional, the investigators found that it had other ‘off-target’ effects – in addition, it blocked the VEGF receptor and disrupted zebrafish blood vessel development, an activity called angiogenesis.In addition, AP26113 exhibited approximately 100-fold selectivity for ALK-positive cell lines compared with an approximate 10-fold selectivity for PF1066, and demonstrated superb properties, including the prospect of once daily oral dosing. We specifically designed AP26113 as a highly powerful and selective inhibitor of ALK with excellent drug-like properties and best-in-class potential, added Clackson. This preclinical work works with our ongoing evaluation of AP26113 as a potential treatment for cancers that communicate ALK. We look forward to shifting AP26113 into clinical trials as soon as possible.