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Screen for Small-Molecule Modulators of Circadian Rhythms Reveals Phenazine as a Redox-State Modifying Clockwork Tuner.
Kelly, Kevin P; Borsetti, Hugo; Wenzler, Marta E; Ustione, Alessandro; Kim, Kwangho; Christov, Plamen P; Ramirez, Bianca; Bauer, Joshua A; Piston, David W; Johnson, Carl Hirschie; Sulikowski, Gary A.
Afiliação
  • Kelly KP; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • Borsetti H; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • Wenzler ME; Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • Ustione A; Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, United States.
  • Kim K; Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • Christov PP; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • Ramirez B; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • Bauer JA; Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • Piston DW; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • Johnson CH; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • Sulikowski GA; Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, United States.
ACS Chem Biol ; 17(7): 1658-1664, 2022 07 15.
Article em En | MEDLINE | ID: mdl-35679588
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenazinas / Ritmo Circadiano Idioma: En Revista: ACS Chem Biol Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenazinas / Ritmo Circadiano Idioma: En Revista: ACS Chem Biol Ano de publicação: 2022 Tipo de documento: Article