LEO 39652, a dual-soft PDE4 inhibitor, demonstrates potent inhibition of PDE4 subtypes A, B, C, and D with respective IC50 values of 1.2 nM, 1.2 nM, 3.0 nM, and 3.8 nM. Additionally, it inhibits TNF-α with an IC50 of 6.0 nM, indicating its potential for topical Atopic dermatitis (AD) research [1].

PDE4C2:3.0 nM (IC50), PDE4A:1.2 nM (IC50), PDE4D:3.8 nM (IC50), PDE4B:1.2 nM (IC50), TNF-α:6.0 nM (IC50)

LEO 39652 exhibits significant unbound in vitro efficacy, as demonstrated by its capacity to inhibit LPS-induced TNF-α release in human peripheral blood mononuclear cells (PBMC) cultured in serum-free medium. Additionally, LEO 39652 demonstrates relatively high affinity for binding to human serum albumin[2].

LEO 39652 is inactivated both in blood and liver (dual-soft) while remaining stable in the skin[1]. Pharmacokinetic analysis reveals that LEO 39652 exhibits total clearance (rats 930, minipigs 200, and monkey 300 mL/min/kg) and ratio to total AUC (rats 4, minipigs 6, and monkey 6%) following intravenous administration (rats 0.075, minipigs 0.5, and monkeys 2.0 mg/kg)[1].