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, by attaching to the PIF-pocket, prompts a shift in the active site residue Lys111, effectively inhibiting aPKCs through an allosteric impact on the enzyme's catalytic process. A pre-treatment of U937 cells with 5 μM PS315 results in a 74% reduction in TNF-α-induced NF-κB activation, with total inhibition achieved at 10 μM PS315. The allosteric inhibitor PS315, along with the N-terminal region of aPKC, directly influences the PIF-pocket on-off switch[1].