The Fourth-Generation Retinoid: Rational Molecular Design of Trifarotene, Selectivity, Efficacy, and Clinical Outcomes

Document Type

Conference Proceeding

Publication Date

7-1-2026

Publication Title

J Am Acad Dermatol

Keywords

Dermatology

Abstract

Trifarotene, a novel topical retinoid, leveraged modern, selective, structure-based design to become the first “fourth-generation” retinoid, targeting retinoic acid receptor gamma (RARγ). The resulting selectivity and growing evidence differentiate its role as a retinoid in the pathophysiology of acne and acne sequelae. This comprehensive review synthesizes current clinical and translational research, describing the unique molecular, pharmacologic, and clinical profile of trifarotene. Mechanistic insights and scientific findings are integrated to provide a framework for understanding the properties of the molecule, as well as avenues for future investigation. Herein, we provide a succinct graphic summary of the totality of clinical and preclinical work on trifarotene, including the molecular design of the fourth-generation retinoid, genetic and cellular analyses, basic research on RAR signaling in the skin, and the ongoing post-approval clinical research program. We clearly outline the current understanding of the molecular profile and structure of trifarotene and the evidence for the consequences of RARγ-specific signaling on the molecular and cellular physiology of the skin, acne efficacy and tolerability, genetic regulation of pathways in inflammation and skin barrier, and progress in addressing persistent challenges in acne treatment, such as the inflammatory acne sequelae of scarring and dyspigmentation.

Volume

95

Issue

1

First Page

AB436

Find It @ Sladen

Share

COinS