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

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

卷:84

Review

Bissonnette, Robert¹  Gold, Linda Stein²  Rubenstein, David S.³  Tallman, Anna M.³  Armstrong, April⁴ 

[1] Innovaderm Res Inc, Montreal, PQ, Canada

[2] Henry Ford Hlth Syst, Detroit, MI USA

[3] Dermavant Sci Inc, Morrisville, NC USA

[4] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90007 USA

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

DOI  :  10.1016/j.jaad.2020.10.085

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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