Evidence map›Paper›PMID 37984928›Full record

ArticleChemMedChem2024

Evaluation of Rhodanine Indolinones as AANAT Inhibitors.

Mackenzie Hagemeister, Luke Hamilton, Nicole Wandrey, Mackinzi Hill, Emery Mounce, Noah Mosel, Katie Lytle, Makenna Redinger, Jake Boley, Nathan Fancher and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Hydantion indolinones as AANAT inhibitors.Bioorganic & medicinal chemistry letters · 2026
    Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Mackenzie HagemeisterDepartment of Psychology, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Luke HamiltonDepartment of Biology, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Nicole WandreyDepartment of Chemistry, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Mackinzi HillDepartment of Chemistry, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Emery MounceDepartment of Psychology, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Noah MoselDepartment of Psychology, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Katie LytleDepartment of Chemistry, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Makenna RedingerDepartment of Chemistry, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Jake BoleyDepartment of Chemistry, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Nathan FancherDepartment of Chemistry, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Alexis HaynesDepartment of Chemistry, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Ianna FillDepartment of Psychology, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Philip A ColeDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Evan HillDepartment of Psychology, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Michael A MoxleyDepartment of Chemistry, University of Nebraska at Kearney, Kearney, NE, 69949, USA.
Allen A ThomasDepartment of Chemistry, University of Nebraska at Kearney, Kearney, NE, 69949, USA.ORCID 0000-0001-8313-0879
University of Nebraska at Kearney · USBrigham and Women's Hospital · US

Funding

UNMC Structural Biology CoreP20GM103427 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PAUL L SORGEN · 2012 to 2026
$59.2M
Chemical Approaches to Understanding Reversible Lysine ModificationsR35GM149229 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI PHILIP A COLE · 2023 to 2026
$1.9M
Serotonin N-Acetyl-Transferase Inhibitors for Circadian Rhythm DisordersR15HL165700 · NHLBI · UNIVERSITY OF NEBRASKA KEARNEY · PI THOMAS, ALLEN · 2022 to 2022
$395k
NHLBI NIH HHS R15 HL165700NIGMS NIH HHS P20 GM103427NIGMS NIH HHS R35 GM149229NIH HHS R35GM149229
6 · The paper itself

Abstract

Circadian rhythm (CR) dysregulation negatively impacts health and contributes to mental disorders. The role of melatonin, a hormone intricately linked to CR, is still a subject of active study. The enzyme arylalkylamine N-acetyltransferase (AANAT) is responsible for melatonin synthesis, and it is a potential target for disorders that involve abnormally high melatonin levels, such as seasonal affective disorder (SAD). Current AANAT inhibitors suffer from poor cell permeability, selectivity, and/or potency. To address the latter, we have employed an X-ray crystal-based model to guide the modification of a previously described AANAT inhibitor, containing a rhodanine-indolinone core. We made various structural modifications to the core structure, including testing the importance of a carboxylic acid group thought to bind in the CoA site, and we evaluated these changes using MD simulations in conjunction with enzymatic assay data. Additionally, we tested three AANAT inhibitors in a zebrafish locomotion model to determine their effects in vivo. Key discoveries were that potency could be modestly improved by replacing a 5-carbon alkyl chain with rings and that the central rhodanine ring could be replaced by other heterocycles and maintain potency.

Indexed as

MelatoninRhodanineAcetyltransferasesAnimalsArylalkylamine N-AcetyltransferaseHumansZebrafishAANAT protein, humanAcetyltransferasesArylalkylamine N-AcetyltransferaseMelatoninRhodanineacetyl transferasecircadian rhythmenzyme modelsheterocyclesmelatonin

Identifiers

PMID37984928
PMCPMC10843758
OpenAlexW4388845851

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.