The selective Syk inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo, and augments the activity of fludarabine in chronic lymphocytic leukemia.
B-cell receptor (BCR) associated kinases including spleen tyrosine kinase (SYK) contribute to the pathogenesis of B-cell malignancies. SYK is persistently phosphorylated in a subset of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), and SYK inhibition results in abrogation of downstream kinase activity and apoptosis.
P505-15 (also known as PRT062607) is a novel, highly selective and orally bioavailable small-molecule SYK inhibitor with anti-SYK activity that is at least 80-fold greater than its affinity for other kinases.
We evaluated the pre-clinical characteristics of P505-15 in models of NHL and CLL. P505-15 successfully inhibited SYK mediated B-cell receptor signaling and decreased cell viability in NHL and CLL.
CLL CANADA: cllcanada.ca