Evidence map›Paper›PMID 41257021›Full record

ArticleACS medicinal chemistry letters2025

Development of Purine and Pyrrolopyrimidine Scaffolds as Potent, Selective, and Brain Penetrant NUAK1 Inhibitors.

Gregory G Aldred, Helen K Boffey, Henriette M G Willems, David Winpenny, Helen Scott, Jonathan H Clarke, 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. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Gregory G AldredThe ALBORADA Drug Discovery Institute, University of Cambridge, Island Research Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, United Kingdom.
Helen K BoffeyThe ALBORADA Drug Discovery Institute, University of Cambridge, Island Research Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, United Kingdom.ORCID https://orcid.org/0000-0001-5088-4615
Henriette M G WillemsThe ALBORADA Drug Discovery Institute, University of Cambridge, Island Research Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, United Kingdom.ORCID https://orcid.org/0000-0001-7196-5975
David WinpennyThe ALBORADA Drug Discovery Institute, University of Cambridge, Island Research Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, United Kingdom.
Helen ScottThe ALBORADA Drug Discovery Institute, University of Cambridge, Island Research Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, United Kingdom.
Jonathan H ClarkeThe ALBORADA Drug Discovery Institute, University of Cambridge, Island Research Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, United Kingdom.ORCID https://orcid.org/0000-0002-4079-5333
Stephen P AndrewsThe ALBORADA Drug Discovery Institute, University of Cambridge, Island Research Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, United Kingdom.ORCID https://orcid.org/0000-0001-6021-6899
John SkidmoreThe ALBORADA Drug Discovery Institute, University of Cambridge, Island Research Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, United Kingdom.ORCID https://orcid.org/0000-0001-9108-7858

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

NUAK1 is a protein kinase with various cellular functions including cell proliferation, migration and adhesion. NUAK1 has also been implicated in tau phosphorylation and stabilization leading to interest in this kinase as a therapeutic target for neurodegenerative disease. Herein, we describe the optimization of the CDK2 inhibitor NU6140 to the potent and selective NUAK1 inhibitor ARUK2010694, with a significantly improved mouse plasma half-life. Further development of this series also led to the discovery of ARUK2010489, a highly brain penetrant NUAK1 inhibitor (unbound brain/plasma ratio in mice (K

Indexed as

ADME propertiesIn vivo profileKinase selectivityNUAK1

Identifiers

PMID41257021
PMCPMC12621045

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.