Ant Venom-Based Ceramide Therapy Is Effective Against Atopic Dermatitis In Vivo.

BACKGROUND:Atopic dermatitis (AD) is a common skin condition with relatively few therapeutic alternatives. These include corticosteroids, which address inflammation but not superinfection, and Januse kinase (JAK) inhibitors, which have a US Food and Drug Administration (FDA) black box for potential carcinogenicity. METHODS:We demonstrate that S14, a synthetic derivative of ant venom-derived solenopsin, has potent anti inflammatory effects on the OVA murine model of atopic dermatitis. S14 has demonstrated prior activity in murine psoriasis and has the benefit of ceramide anti-inflammatory effects without being able to be metabolized into proinflammatory sphingosine-1 phosphate. RESULTS:The efficacy of S14 accompanied by the induction of IL-12 suggests a commonality in inflammatory skin disorders, and our results suggest that pharmacological ceramide restoration will be broadly effective for inflammatory skin disease. CONCLUSIONS:Solenopsin derivative S14 has anti-inflammatory effects in murine models of AD and psoriasis. This makes S14 a strong candidate for human use, and pre-IND studies are warranted.J Drugs Dermatol. 2023;22(10):1001-1006 doi:10.36849/JDD.7308.