IC50: 0.7 nM (PDE8A), less than 0.3 nM (PDE8B)

PF-04957325 is over two orders of magnitude less efficient than PICL in suppressing polyclonal Teff cell proliferation, and shows no effect on cytokine gene expression in these cells, despite its robust effect on T cell adhesion. PF-04957325 is a selective PDE8 inhibitor and inhibits breast cancer cell migration. PF-04957325 greatly potentiates steroidogenesis in WT adrenal cells. PF-04957325 shows a reported IC ₅₀ of 0.7 nM against PDE8A, 0.2 nM against PDE8B, and > 1.5 μM against all other PDE isoforms. PF-04957325 treatment of WT Leydig cells or MA10 cells increases steroid production but has no effect in PDE8A (-/-)/B(-/-) double-knockout cells, confirming the selectivity of the drug. Moreover, under basal conditions, cotreatment with PF-04957325 plus rolipram, a PDE4-selective inhibitor, synergistically potentiates steroid production.