Topically Applied “Small Molecules”: Janus Kinases or PDE-4 as Targets?

Intracellular target structures have gained importance as therapeutic targets for small-molecule therapeutics in atopic dermatitis (AD), and topical formulation ensures a localized pharmacological effect, thereby promoting a favorable safety profile [1,2]. In some countries, topical Janus kinase (JAK) inhibitors have cleared regulatory hurdles for the treatment of AD—for example, delgocitinib is approved in Japan, and ruxolitinib has recently been approved in the EU in addition to the United States. Among topical phosphodiesterase (PDE)-4 inhibitors, in addition to crisaborol and roflumilast, difamilast has also recently received FDA approval.