TGX-221 is a p110β-specific inhibitor with IC50 of 5 nM, 1000-fold more selective for p110β than p110α.

Phosphatidylinositol 3-kinase (PI3K) catalyzes the phosphorylation of phosphatidylinositol at the 3 position to produce the second messengers phosphatidylinositol-(3,4)-bisphosphate (PtdIns-(3,4)-P2) and PtdIns-(3,4,5)-P3).Class 1 PI3Ks are composed of a p110 catalytic subunit, of which there are 4 isoforms (p110α, p110β, p110δ, and p100γ), and a p85 regulatory subunit.TGX-221 is a potent, selective, and cell permeable inhibitor of PI3K p110β.Inhibition appears to occur at the ATP binding site based on the observed increase in IC50 from 5 to ~50 nM at ATP concentrations of 50 µM and 1 mM, respectively. TGX-221 inhibits PtdIns-(3,4)-P2 production in platelets with an IC50 of 50 nM.Selective inhibition of PI3K p110β results in defective platelet thrombus formation and defines PI3K as a target for antithrombotic therapy.