Evidence map›Paper›PMID 35731924›Full record

ArticleACS chemical neuroscience2022

Structural Analysis and Development of Notum Fragment Screening Hits.

Yuguang Zhao, William Mahy, Nicky J Willis, Hannah L Woodward, David Steadman, Elliott D Bayle, Benjamin N Atkinson, James Sipthorp, Luca Vecchia, Reinis R Ruza and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS chemical neuroscience, 2022. 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
–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

3 citing papers in PubMed.

  1. 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

21 authors.

Yuguang ZhaoDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.ORCID 0000-0001-8916-8552
William MahyAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.
Nicky J WillisAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.ORCID 0000-0003-3245-5280
Hannah L WoodwardAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.ORCID 0000-0001-8429-2546
David SteadmanAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.ORCID 0000-0003-4271-5525
Elliott D BayleAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.
Benjamin N AtkinsonAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.ORCID 0000-0001-5511-9859
James SipthorpAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.
Luca VecchiaDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.
Reinis R RuzaDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.
Karl HarlosDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.
Fiona JeganathanAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.
Stefan ConstantinouAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.
Artur CostaAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.
Svend KjærThe Francis Crick Institute, 1 Midland Road, Kings Cross, London NW1 1AT, U.K.
Magda BictashAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.
Patricia C SalinasDepartment of Cell and Developmental Biology, Laboratory for Molecular and Cellular Biology, University College London, London WC1E 6BT, U.K.
Paul WhitingAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.
Jean-Paul VincentThe Francis Crick Institute, 1 Midland Road, Kings Cross, London NW1 1AT, U.K.
Paul V FishAlzheimer's Research UK UCL Drug Discovery Institute, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, U.K.ORCID 0000-0002-2117-2173
E Yvonne JonesDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.ORCID 0000-0002-3834-1893

Funding

Cancer Research UK 17721Cancer Research UK FC001002Wellcome Trust FC001002
6 · The paper itself

Abstract

The Wnt signaling suppressor Notum is a promising target for osteoporosis, Alzheimer's disease, and colorectal cancers. To develop novel Notum inhibitors, we used an X-ray crystallographic fragment screen with the Diamond-SGC Poised Library (DSPL) and identified 59 fragment hits from the analysis of 768 data sets. Fifty-eight of the hits were found bound at the enzyme catalytic pocket with potencies ranging from 0.5 to >1000 μM. Analysis of the fragments' diverse binding modes, enzymatic inhibitory activities, and chemical properties led to the selection of six hits for optimization, and five of these resulted in improved Notum inhibitory potencies. One hit, 1

Indexed as

Crystallography, X-RayDiamond-SGC Poised Library (DSPL)fragment screeninghit-to-lead developmentNotum inhibitorsWnt signaling

Identifiers

PMID35731924
PMCPMC9264368

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.