Tapinarof

Tapinarof (WBI-1001) is a natural aryl hydrocarbon receptor (AhR) agonist with an EC₅₀ of 13 nM. Tapinarof resolves skin inflammation in mice^[1]. IC50 & Target: EC50: 13 nM (AhR)^[1] In Vitro: Tapinarof activates the AhR pathway through direct binding. Tapinarof dose-dependently induces nuclear translocation of AhR in immortalized keratinocytes (HaCaT) (EC₅₀=0.16 nM)^[1]. In Vivo: Tapinarof acts through AhR to reduce inflammation in IMQ-treated mice. AhR-sufficient mice on a C57Bl/6 background exhibit a reduced clinical score after treatment with Tapinarof or 6-formylindolo(3,2-b)carbazole (FICZ). In contrast, AhR KO mice do not respond to the anti-inflammatory effects of Tapinarof. FICZ is used as a comparator in these studies and yields similar results, with dramatically reduced inflammatory responses in wild-type, but not AhR KO mice^[1].