The transcriptional repressor REV-ERB as a novel target for disease

Bioorg Med Chem Lett. 2020 Sep 1;30(17):127395. doi: 10.1016/j.bmcl.2020.127395. Epub 2020 Jul 10.

Abstract

REV-ERB is a member of the nuclear receptor superfamily of transcription factors involved in the regulation of many physiological processes, from circadian rhythm, to immune function and metabolism. Accordingly, REV-ERB has been considered as a promising, but difficult drug target for the treatment of numerous diseases. Here, we concisely review current understanding of the function of REV-ERB, modulation by endogenous factors and synthetic ligands, and the involvement of REV-ERB in select human diseases. Particular focus is placed on the medicinal chemistry of synthetic REV-ERB ligands, which demonstrates the need for higher quality ligands to aid in robust validation of this exciting target.

Keywords: Drug development; REV-ERB; Transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Circadian Rhythm / physiology
  • Heme / chemistry
  • Humans
  • Immune System Diseases / metabolism
  • Immune System Diseases / pathology
  • Ligands
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / agonists
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / antagonists & inhibitors
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Repressor Proteins / agonists
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Ligands
  • NR1D1 protein, human
  • NR1D2 protein, human
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • Heme