2. Academic Validation
  3. Screen for Small-Molecule Modulators of Circadian Rhythms Reveals Phenazine as a Redox-State Modifying Clockwork Tuner

Screen for Small-Molecule Modulators of Circadian Rhythms Reveals Phenazine as a Redox-State Modifying Clockwork Tuner

  • ACS Chem Biol. 2022 Jul 15;17(7):1658-1664. doi: 10.1021/acschembio.2c00240.
Kevin P Kelly 1,  Hugo Borsetti 1,  Marta E Wenzler 2,  Alessandro Ustione 3,  Kwangho Kim 2 4,  Plamen P Christov 4,  Bianca Ramirez 2,  Joshua A Bauer 4 5,  David W Piston 3,  Carl Hirschie Johnson 1 4,  Gary A Sulikowski 2 4
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • 2 Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • 3 Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, United States.
  • 4 Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • 5 Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.
PMID: 35679588 DOI: 10.1021/acschembio.2c00240
Abstract

A high-throughput cell-based screen identified redox-active small molecules that produce a period lengthening of the circadian rhythm. The strongest period lengthening phenotype was induced by a phenazine carboxamide (VU661). Comparison to two isomeric benzquinoline carboxamides (VU673 and VU164) shows the activity is associated with the redox modulating phenazine functionality. Furthermore, ex vivo Cell Analysis using optical redox ratio measurements shows the period lengthening phenotype to be associated with a shift to the NAD/FAD oxidation state of nicotinamide and flavine coenzymes.

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