An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals

Jun 6, 2020Cell chemical biology

A Selective Cryptochrome 1 Modulator Influences Mammal Daily Biological Rhythms

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Circadian BiologyCircadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

A small-molecule modulator, KL201, selectively stabilizes CRY1 and lengthens circadian rhythms in cells and tissues.

  • KL201 was identified through cell-based circadian chemical screening.
  • The compound specifically stabilizes CRY1 without affecting CRY2.
  • A structure-activity relationship study revealed important interaction sites for CRY1 regulation.
  • KL201 binds to CRY1 in a region overlapping with FBXL3, a component of the ubiquitin ligase complex.
  • The effect of KL201 on circadian rhythms is reduced when FBXL3 is knocked down.

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