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Findings
What does this study add?
- At a concentration of 308 nM, orismilast inhibited the PDE4 catalytic domain by 84%; other PDE enzymes tested were inhibited by 0–18%.
- Orismilast inhibited TNFα release 5-times more potently than apremilast in PBMC (IC50 10 nM versus 52 nM, respectively).
- Orismilast inhibited TNFα release 14-times more potently in whole blood (IC50 30 nM versus 432 nM).
- Oral orismilast reduced ear thickness in an oxazolone mouse model of chronic skin inflammation in a dose-dependent manner.
- Dosing with 0.1 mg/kg and 0.3 mg/kg decreased ear thickness, albeit not significantly.
- Oral orismilast 1 mg/kg and 10 mg/kg resulted in significant ear thickness reduction over time (p<0.01 and p<0.001, respectively).
- Reduction in ear thickness with oral orismilast was comparable to that of dexamethasone.
