Evidence mapPaperPMID 37872245Full record

ArticleScientific reports2023

Binding mechanism and biological effects of flavone DYRK1A inhibitors for the design of new antidiabetics.

Katarzyna Pustelny, Przemyslaw Grygier, Agata Barzowska, Barbara Pucelik, Alex Matsuda, Krzysztof Mrowiec, Emilia Slugocka, Grzegorz M Popowicz, Grzegorz Dubin, Anna Czarna

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. 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 22% 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. Article
  2. Article
  3. Review
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

10 authors at 2 institutions in 2 countries.

Katarzyna PustelnyMalopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-387, Krakow, Poland.
Przemyslaw GrygierDoctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland.
Agata BarzowskaDoctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland.
Barbara PucelikMalopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-387, Krakow, Poland.
Alex MatsudaDoctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland.
Krzysztof MrowiecDoctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland.
Emilia SlugockaDoctoral School of Medical and Health Sciences, Jagiellonian University Medical College, Krakow, Poland.
Grzegorz M PopowiczInstitute of Structural Biology, Helmholtz Zentrum Munchen, Neuherberg, Germany.
Grzegorz DubinMalopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-387, Krakow, Poland.
Anna CzarnaMalopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-387, Krakow, Poland. anna1.czarna@uj.edu.pl.
Jagiellonian University · PLHelmholtz Zentrum München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The selective inhibition of kinases from the diabetic kinome is known to promote the regeneration of beta cells and provide an opportunity for the curative treatment of diabetes. The effect can be achieved by carefully tailoring the selectivity of inhibitor toward a particular kinase, especially DYRK1A, previously associated with Down syndrome and Alzheimer's disease. Recently DYRK1A inhibition has been shown to promote both insulin secretion and beta cells proliferation. Here, we show that commonly available flavones are effective inhibitors of DYRK1A. The observed biochemical activity of flavone compounds is confirmed by crystal structures solved at 2.06 Å and 2.32 Å resolution, deciphering the way inhibitors bind in the ATP-binding pocket of the kinase, which is driven by the arrangement of hydroxyl moieties. We also demonstrate antidiabetic properties of these biomolecules and prove that they could be further improved by therapy combined with TGF-β inhibitors. Our data will allow future structure-based optimization of the presented scaffolds toward potent, bioavailable and selective anti-diabetic drugs.

Indexed as

Alzheimer DiseaseFlavonesCell ProliferationHumansHypoglycemic AgentsProtein Kinase InhibitorsflavoneFlavonesHypoglycemic AgentsProtein Kinase Inhibitors

Identifiers

PMID37872245
PMCPMC10593742
OpenAlexW4387880617

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.