@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.}",
note = "Funding Information: We thank J. Hogenesch (Cincinnati Children{\textquoteright}s Hospital Medical Center) for supplying Bmal1-dLuc U2OS cells used in assays. D. Weaver assisted with the HTS experiments performed in the Vanderbilt High-Throughput Screening Core Facility. The HTS Core receives support from the Vanderbilt Institute of Chemical Biology and the Vanderbilt Ingram Cancer Center (P30 CA68485). This work was supported by the National Institutes of Health (R37 GM067152, R21 NS054991, and R21 MH082258) and the Vanderbilt Institute of Chemical Biology. B.R. acknowledges the support of the Vanderbilt NSF-REU program (CHE 0850976). J.A.B. acknowledges the support from the NCI in the form of a Research Specialist Award (R50 CA211206). Funds from the NIH to purchase the Integrated Confocal ImageXpress High-Content Screening System are acknowledged (S10 OD028719). Publisher Copyright: {\textcopyright} 2022 American Chemical Society. All rights reserved.",
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",
}