Evidence map›Paper›PMID 39967649›Full record

ArticleACS medicinal chemistry letters2025

Development of the Pyrido[2,3-

Timothy P C Rooney, Gregory G Aldred, David Winpenny, Helen Scott, Henriette M G Willems, Iryna Voytyuk, Jonathan H Clarke, Helen K Boffey, Stephen P Andrews, John Skidmore

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

10 authors.

Timothy P C RooneyThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.ORCID https://orcid.org/0000-0001-6788-5526
Gregory G AldredThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.
David WinpennyThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.
Helen ScottThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.
Henriette M G WillemsThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.ORCID https://orcid.org/0000-0001-7196-5975
Iryna VoytyukThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.
Jonathan H ClarkeThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.ORCID https://orcid.org/0000-0002-4079-5333
Helen K BoffeyThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.ORCID https://orcid.org/0000-0001-5088-4615
Stephen P AndrewsThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.ORCID https://orcid.org/0000-0001-6021-6899
John SkidmoreThe ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge CB2 0AH, U.K.ORCID https://orcid.org/0000-0001-9108-7858

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The protein kinase NUAK1 has been implicated in various biological functions including cell adhesion, migration and proliferation. Genetic reduction of NUAK1 expression has notably been shown to lower total levels of human tau in a tauopathy mouse model, identifying this kinase as a potential therapeutic target for neurodegenerative disease. In this paper, we describe improvement of the NUAK1 potency, kinase-selectivity and pharmacokinetic properties of the brain-penetrant but unselective CDK4/CDK6/NUAK1 inhibitor ON123300. Through a scaffold-optimization approach we have identified different chemotypes delivering NUAK1 inhibition with improved potency and selectivity over CDK kinases compared with ON123300. We present ADME profiling and in vivo pharmacokinetic data for these compounds.

Identifiers

PMID39967649
PMCPMC11831560

What OpenQuestion holds

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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.