BLU-808, a Potent and Selective Small Molecule Inhibitor of Wild-type c-KIT for Mast Cell Disorders

C-KIT is a receptor tyrosine kinase which is essential for mast cell activation, proliferation, chemotaxis, and survival. Several inflammatory disorders are characterized by inappropriate activation and/or proliferation of mast cells, including systemic mastocytosis, where approximately 95% of patients present with a KIT D816V mutation. Other inflammatory diseases such as chronic urticaria are driven by inappropriate activation of mast cells but are wild-type (wt) for c-KIT, suggesting these patients could benefit from oral wt c-KIT targeted therapy.