PS315 inhibits the full-length and catalytic domain constructs of PKCζ (IC50=10 μM) and PKCη (IC50=30 μM). PS315 has anti-cancer activity. PS315 is a derivative of PS48 and is an allosteric PKC inhibitor by binding to the PIF-pocket of aPKC and inducing displacement of the active site residue Lys111.

PKCη:30 μM, PKCζ:10 μM

PS315, binding at the PIF-pocket, induces a displacement of the active site residue Lys111, thereby inhibiting the activity of aPKCs by allosterically affecting the catalytic mechanism of the kinase. Preincubation of U937 cells with 5 μM PS315 inhibits TNF-α caused NF-κB activation by 74%, whereas complete inhibition is observed with 10 μM PS315. The small allosteric inhibitor PS315 and the N-terminal region of aPKC both act directly on the PIF-pocket on-off switch[1].