Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent

J Am Acad Dermatol. 2021 Apr;84(4):1059-1067. doi: 10.1016/j.jaad.2020.10.085. Epub 2020 Nov 3.


Tapinarof, a novel, first-in-class, small-molecule topical therapeutic aryl hydrocarbon receptor (AhR)-modulating agent, is in clinical development for the treatment of psoriasis and atopic dermatitis. The efficacy of tapinarof in psoriasis is attributed to its specific binding and activation of AhR, a ligand-dependent transcription factor, leading to the downregulation of proinflammatory cytokines, including interleukin 17, and regulation of skin barrier protein expression to promote skin barrier normalization. AhR signaling regulates gene expression in immune cells and skin cells and has critical roles in the regulation of skin homeostasis. Tapinarof-mediated AhR signaling underlies the mechanistic basis for the significant efficacy and acceptable tolerability observed in early-phase clinical trials of tapinarof cream in the treatment of psoriasis.

Keywords: Antioxidant; T cell; aryl hydrocarbon receptor (AhR); cytokines; dermis; epidermis; homeostasis; immune; inflammation; ligand; psoriasis; small molecule; tapinarof; therapeutic aryl hydrocarbon receptor–modulating agent (TAMA); topical; transcription factor.

Publication types

  • Review

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / drug effects*
  • Clinical Trials as Topic
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / genetics
  • Keratinocytes / drug effects
  • Oxidative Stress
  • Psoriasis / drug therapy*
  • Psoriasis / genetics
  • Receptors, Aryl Hydrocarbon / drug effects*
  • Resorcinols / pharmacology
  • Resorcinols / therapeutic use*
  • Skin / drug effects
  • Skin / immunology
  • Skin / pathology
  • Skin Absorption / drug effects
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*


  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Interleukin-17
  • Receptors, Aryl Hydrocarbon
  • Resorcinols
  • Stilbenes
  • tapinarof