Download The Selective p110 Inhibitor IPI-3063 Potently Suppresses B Cell

The Selective p110 Inhibitor IPI-3063 Potently Suppresses B Cell Survival and Proliferation
Annie Mai
Mentor: David Fruman
The phosphoinositide-3-kinase (PI3K) signaling pathway is a crucial pathway that is involved in many cellular
processes such as differentiation, proliferation and cell survival. The p110δ catalytic isoform of PI3K is
critical for these cellular processes in B lymphocytes. Elevated PI3K signaling, however, is often associated
with B cell malignancies or lymphocyte hyperactivation found in patients with autoimmune disease. Thus, this
pathway is an attractive target for cancer and autoimmune therapies. In this study, we tested the effects of
novel inhibitors of p110δ and p110γ in assays of B cell function. IPI-3063, a selective p110δ inhibitor, was
found to be potent in reducing proliferation and survival of B cells, comparable to the pan-PI3K inhibitor.
On the other hand, AS252424, an inhibitor for p110𝛾, showed little or no effect on B cell function. In
addition, a dual inhibitor for both isoforms, IPI-443, exhibited a similar B cell response when compared to
p110δ inhibition alone. This data suggest that p110δ is the dominant isoform in regulating B cell responses
and inhibiting p110δ alone is sufficient to disrupt their function. Together, these findings demonstrated that
IPI-3063 and IPI-443 are useful research tools in studying the p110δ and p110γ isoforms in immune cells.