**Background**
Psoriasis (Ps) and atopic dermatitis (AD) are chronic inflammatory skin conditions characterized by the overproduction of pro-inflammatory cytokines and the infiltration of immune cells into the dermis. Phosphodiesterase 4 (PDE4) is a key enzyme that degrades cyclic adenosine monophosphate (cAMP); its inhibition leads to increased intracellular cAMP levels, which subsequently suppresses the production of various inflammatory mediators. Given the central role of PDE4 in regulating the immune response in the skin, it has become a primary therapeutic target for treating these inflammatory disorders. In this context, we will introduce a potent boron-containing anti-inflammatory compound – Crisaborole.
**Definition**
Crisaborole (also known as AN-2728) is a potent inhibitor of PDE4 and cytokine release, exhibiting an IC50 value of 0.49 μM against PDE4 in human U937 cells.
**In Vitro and In Vivo Studies**
According to the Crisaborole description, this compound is a benzoxaborole derivative. Crystallography indicates that the interaction of benzoxaboroles with the hydrophobic pocket in the PDE4 catalytic domain increases their affinity for the enzyme. Crisaborole in vitro studies demonstrate that it inhibits PDE4, TNF-α, IL-2, IFN-γ, IL-5, and IL-10 with IC50 values of 0.49, 0.54, 0.61, 0.83, 2.4, and 5.3 μM, respectively. Specifically, in human PBMC cells, Crisaborole inhibits LPS-induced TNF-alpha production (EC50 = 0.53 μM) and phytohemagglutinin-induced release of IL-2 (IC50 = 0.61 μM) and IFN-gamma (IC50 = 0.83 μM). While showing the most potent activity against the PDE4 catalytic domain (IC50 = 0.11 μM in Sf9 cells), it also inhibits PDE7A1 (IC50 = 0.73 μM), PDE1A3 (IC50 = 6.1 μM), and PDE3Cat (IC50 = 6.4 μM).
Regarding Crisaborole In Vivo activity, the compound shows significant inhibition of ear edema caused by phorbol ester after dosing at 1 mg/ear×2 (78% and 68% inhibition, respectively). This efficacy is comparable to that of dexamethasone, indicating strong anti-inflammatory activity and excellent skin penetration. Furthermore, clinical trials report that Crisaborole is well tolerated and demonstrates significant effects on markers of efficacy. For researchers seeking detailed Crisaborole technical information, these results highlight its potential as a topical treatment for skin inflammation. In conclusion, Crisaborole is a potent PDE4 inhibitor that suppresses the release of TNF-α, IL-12, IL-23, and other cytokines associated with psoriasis and atopic dermatitis.
Keywords
Crisaborole, 906673-24-3, AN-2728, PF-06930164, AN2728, AN 2728, PF06930164, PF 06930164, Phosphodiesterase (PDE), Inhibitor, inhibitor, inhibit
References
[1] Akama T, et al. Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2129-32.
[2] Nazarian R, et al. AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis. Curr Opin Investig Drugs. 2009 Nov;10(11):1236-42.