Structure-based design of Trifarotene (CD5789), a potent and selective RARγ agonist for the treatment of acne

Bioorg Med Chem Lett. 2018 Jun 1;28(10):1736-1741. doi: 10.1016/j.bmcl.2018.04.036. Epub 2018 Apr 15.

Abstract

Retinoids have a dominant role in topical acne therapy and to date, only RARβ and RARγ dual agonists have reached the market. Given the tissue distribution of RAR isoforms, it was hypothesized that developing RARγ -selective agonists could yield a new generation of topical acne treatments that would increase safety margins while maintaining the robust efficacy of previous drugs. Structural knowledge derived from the X-ray structure of known γ-selective CD437, suggested the design of a novel triaryl series of agonists which was optimized and ultimately led to the discovery of Trifarotene/CD5789.

Keywords: Acne; CD437; CD5789; RARγ; Trifarotene.

MeSH terms

  • Acne Vulgaris / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Receptors, Retinoic Acid / agonists*
  • Retinoids / chemical synthesis
  • Retinoids / chemistry
  • Retinoids / pharmacology*
  • Structure-Activity Relationship

Substances

  • Receptors, Retinoic Acid
  • Retinoids
  • retinoic acid receptor gamma
  • trifarotene