Evidence map›Paper›PMID 37564419›Full record

ArticleChemical science2023

Fragment expansion with NUDELs - poised DNA-encoded libraries.

Catherine L A Salvini, Benoit Darlot, Jack Davison, Mathew P Martin, Susan J Tudhope, Shannon Turberville, Akane Kawamura, Martin E M Noble, Stephen R Wedge, James J Crawford and 1 more

Open access · diamondAbstract read
In one paragraph

Article in Chemical science, 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
1.5field-weighted citation impact, top 17% 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, 10 citations in OpenAlex.

  1. Review
  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

11 authors at 3 institutions in 2 countries.

Catherine L A SalviniCancer Research Horizons Therapeutic Innovation Newcastle Drug Discovery Group, Chemistry, School of Natural and Environmental Sciences, Newcastle University Bedson Building NE1 7RU UK mike.waring@ncl.ac.uk.
Benoit DarlotChemistry, School of Natural and Environmental Sciences, Newcastle University Bedson Building NE1 7RU UK.
Jack DavisonCancer Research Horizons Therapeutic Innovation Newcastle Drug Discovery Group, Chemistry, School of Natural and Environmental Sciences, Newcastle University Bedson Building NE1 7RU UK mike.waring@ncl.ac.uk.
Mathew P MartinCancer Research Horizons Therapeutic Innovation Newcastle Drug Discovery Group, Translational and Clinical Research Institute, Newcastle University Paul O'Gorman Building NE2 4HH UK.
Susan J TudhopeCancer Research Horizons Therapeutic Innovation Newcastle Drug Discovery Group, Translational and Clinical Research Institute, Newcastle University Paul O'Gorman Building NE2 4HH UK.
Shannon TurbervilleCancer Research Horizons Therapeutic Innovation Newcastle Drug Discovery Group, Translational and Clinical Research Institute, Newcastle University Paul O'Gorman Building NE2 4HH UK.
Akane KawamuraChemistry, School of Natural and Environmental Sciences, Newcastle University Bedson Building NE1 7RU UK.
Martin E M NobleCancer Research Horizons Therapeutic Innovation Newcastle Drug Discovery Group, Translational and Clinical Research Institute, Newcastle University Paul O'Gorman Building NE2 4HH UK.
Stephen R WedgeCancer Research Horizons Therapeutic Innovation Newcastle Drug Discovery Group, Translational and Clinical Research Institute, Newcastle University Paul O'Gorman Building NE2 4HH UK.
James J CrawfordGenentech Inc. 1 DNA Way South San Francisco California 94080 USA.ORCID https://orcid.org/0000-0002-6408-8246
Michael J WaringCancer Research Horizons Therapeutic Innovation Newcastle Drug Discovery Group, Chemistry, School of Natural and Environmental Sciences, Newcastle University Bedson Building NE1 7RU UK mike.waring@ncl.ac.uk.ORCID https://orcid.org/0000-0002-9110-8783
Newcastle University · GBUniversity of Oxford · GBGenesys (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Optimisation of the affinity of lead compounds is a critical challenge in the identification of drug candidates and chemical probes and is a process that takes many years. Fragment-based drug discovery has become established as one of the methods of choice for drug discovery starting with small, low affinity compounds. Due to their low affinity, the evolution of fragments to desirable levels of affinity is often a key challenge. The accepted best method for increasing the potency of fragments is by iterative fragment growing, which can be very time consuming and complex. Here, we introduce a paradigm for fragment hit optimisation using poised DNA-encoded chemical libraries (DELs). The synthesis of a poised DEL, a partially constructed library that retains a reactive handle, allows the coupling of any active fragment for a specific target protein, allowing rapid discovery of potent ligands. This is illustrated for bromodomain-containing protein 4 (BRD4), in which a weakly binding fragment was coupled to a 42-member poised DEL

Identifiers

PMID37564419
PMCPMC10411621
OpenAlexW4384079389

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.