Tapinarof activates the AhR pathway through direct binding. Tapinarof dose-dependently induces nuclear translocation of AhR in immortalized keratinocytes (HaCaT) (EC ₅₀ =0.16 nM).

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.