Entospletinib (GS-9973)

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase that upon phosphorylation binds to immunoreceptor tyrosine-based activation motifs of FcRγ chains and mediates downstream signaling related to platelet function and inflammation. GS-9973 is a potent Syk inhibitor (IC₅₀ = 7.7 nM) that demonstrates 10-35-fold selectivity for Syk over a panel of 359 nonmutant kinases. In conjunction with the PI3Kδ inhibitor CAL-101 , it has been used to reduce chronic lymphocytic leukemia cell survival and to disrupt chemokine signaling at nanomolar concentrations.

GS 9973 is a selective and orally bioavailable inhibitor of spleen tyrosine kinase (Syk).