XL499

XL499 is a potent and selective inhibitor of PI3Kδ, a class 1A PI3K isoform expressed primarily in hematopoietic cells and some hematologic malignancies. PI3Kδ plays important roles in various aspects of immune cell function, including mast cell degranulation, B lymphocyte maturation, and T lymphocyte differentiation. Targeting PI3Kδ signaling has been shown to significantly reduce inflammation and disease progression in preclinical models of rheumatoid arthritis and allergic asthma. In addition, selectively targeting PI3Kδ has been shown to lead to clinically relevant responses in some lymphoma patients. XL499 was advanced to development candidate status in January 2010.