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

Kevin P. Kelly; Hugo Borsetti; Marta E. Wenzler; Alessandro Ustione; Kwangho Kim; Plamen P. Christov; Bianca Ramirez; Joshua A. Bauer; David W. Piston; Carl Hirschie Johnson; Gary A. Sulikowski

doi:10.1021/acschembio.2c00240

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

Kevin P. Kelly, Hugo Borsetti, Marta E. Wenzler, Alessandro Ustione, Kwangho Kim, Plamen P. Christov, Bianca Ramirez, Joshua A. Bauer, David W. Piston, Carl Hirschie Johnson, Gary A. Sulikowski

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English
Pages (from-to)	1658-1664
Number of pages	7
Journal	ACS Chemical Biology
Volume	17
Issue number	7
DOIs	https://doi.org/10.1021/acschembio.2c00240
State	Published - Jul 15 2022

Access to Document

10.1021/acschembio.2c00240

Cite this

Kelly, K. P., Borsetti, H., Wenzler, M. E., Ustione, A., Kim, K., Christov, P. P., Ramirez, B., Bauer, J. A., Piston, D. W., Johnson, C. H., & Sulikowski, G. A. (2022). Screen for Small-Molecule Modulators of Circadian Rhythms Reveals Phenazine as a Redox-State Modifying Clockwork Tuner. ACS Chemical Biology, 17(7), 1658-1664. https://doi.org/10.1021/acschembio.2c00240

@article{285a7ea7356f4bfb854540382f79df05,

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

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.",

author = "Kelly, {Kevin P.} and Hugo Borsetti and Wenzler, {Marta E.} and Alessandro Ustione and Kwangho Kim and Christov, {Plamen P.} and Bianca Ramirez and Bauer, {Joshua A.} and Piston, {David W.} and Johnson, {Carl Hirschie} and Sulikowski, {Gary A.}",

year = "2022",

month = jul,

day = "15",

doi = "10.1021/acschembio.2c00240",

language = "English",

volume = "17",

pages = "1658--1664",

journal = "ACS Chemical Biology",

issn = "1554-8929",

number = "7",

}

TY - JOUR

T1 - Screen for Small-Molecule Modulators of Circadian Rhythms Reveals Phenazine as a Redox-State Modifying Clockwork Tuner

AU - Kelly, Kevin P.

AU - Borsetti, Hugo

AU - Wenzler, Marta E.

AU - Ustione, Alessandro

AU - Kim, Kwangho

AU - Christov, Plamen P.

AU - Ramirez, Bianca

AU - Bauer, Joshua A.

AU - Piston, David W.

AU - Johnson, Carl Hirschie

AU - Sulikowski, Gary A.

PY - 2022/7/15

Y1 - 2022/7/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85133501773&partnerID=8YFLogxK

U2 - 10.1021/acschembio.2c00240

DO - 10.1021/acschembio.2c00240

M3 - Article

C2 - 35679588

AN - SCOPUS:85133501773

SN - 1554-8929

VL - 17

SP - 1658

EP - 1664

JO - ACS Chemical Biology

JF - ACS Chemical Biology

IS - 7

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this