Combating Autoimmune Diseases With Retinoic Acid Receptor-Related Orphan Receptor-γ (RORγ or RORc) Inhibitors: Hits and Misses

J Med Chem. 2018 Dec 27;61(24):10976-10995. doi: 10.1021/acs.jmedchem.8b00588. Epub 2018 Jul 30.

Abstract

The nuclear receptor retinoic acid receptor-related orphan receptor gamma (RORγ or RORc) is a key transcription factor for the production of pro-inflammatory cytokines implicated in the pathogenesis of autoimmune diseases. Recently, small molecule inhibitors of RORc drew the enormous attention of the research community worldwide as a possible therapy for autoimmune diseases, mediated by the IL-17 cytokine. With the clinical proof-of-concept inferred from a small molecule inhibitor VTP-43742 for psoriasis and recent inflow of several RORc inhibitors into the clinic for therapeutic interventions in autoimmune diseases, this field continues to evolve. This review briefly summarizes the RORc inhibitors disclosed in the literature and discusses the progress made by these inhibitors in combating autoimmune diseases.

Publication types

  • Review

MeSH terms

  • Amides / chemistry
  • Amides / pharmacology
  • Autoimmune Diseases / drug therapy*
  • Clinical Trials as Topic
  • Humans
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / antagonists & inhibitors*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / chemistry
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology

Substances

  • Amides
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Pyridines
  • Pyrrolidines
  • RORC protein, human
  • Sulfonamides
  • VTP-43742