Orismilast (LEO-32731) is a potent, selective, second generation PDE4 inhibitor with IC50 values of 3-52 nM for PDE4A/4B/4D subtype splice variants.
Orismilast (LEO-32731) potently inhibits all PDE4B and PDE4D subtype splice variants compared to apremilast and demonstrates reduced potency for the PDE4C2 subtype and PDE4A10 subtype compared to other PDE4 subtypes with an IC50 of approximately 104 nM and 52
nM, respectively.
Orismilast (LEO-32731) is a 5 times more potent inhibitor of LPS-induced TNFα release in PBMC (IC50=2 nM) and a 14 times more potent inhibitor of aCD3/aCD28 induced TNFα release in human whole blood.
Orismilast (LEO-32731) inhibits the secretion of cytokines across all investigated T-helper cell sublineages, with most the profound effect on Th1-cell effector cytokines but also demonstrates potent inhibition on Th17 cells and Th2 cells related cytokines.
Orismilast (LEO-32731) (10 mg/kg and 30 mg/kg, oral) significantly reduced ear thickness and inflammation markers in vivo in the murine chronic oxazolone mouse model.