Evidence map›Paper›PMID 38949112›Full record

ArticleJournal of medicinal chemistry2024

Occurrence of "Natural Selection" in Successful Small Molecule Drug Discovery.

A Lina Heinzke, Axel Pahl, Barbara Zdrazil, Andrew R Leach, Herbert Waldmann, Robert J Young, Paul D Leeson

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. 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

7 authors.

A Lina HeinzkeEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton CB10 1SD, Cambridgeshire, U.K.ORCID 0000-0002-8303-4243
Axel PahlCompound Management and Screening Center, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany.
Barbara ZdrazilEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton CB10 1SD, Cambridgeshire, U.K.ORCID 0000-0001-9395-1515
Andrew R LeachEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton CB10 1SD, Cambridgeshire, U.K.
Herbert WaldmannDepartment of Chemical Biology, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany.ORCID 0000-0002-9606-7247
Robert J YoungBlue Burgundy Ltd., Ampthill, Bedfordshire MK45 2AD, U.K.
Paul D LeesonPaul Leeson Consulting Ltd., Nuneaton CV13 6LZ, Warwickshire, U.K.ORCID 0000-0003-0212-3437

Funding

Wellcome Trust
6 · The paper itself

Abstract

Published compounds from ChEMBL version 32 are used to seek evidence for the occurrence of "natural selection" in drug discovery. Three measures of natural product (NP) character were applied, to compare time- and target-matched compounds reaching the clinic (clinical compounds in phase 1-3 development and approved drugs) with background compounds (reference compounds). Pseudo-NPs (PNPs), containing NP fragments combined in ways inaccessible by nature, are increasing over time, reaching 67% of clinical compounds first disclosed since 2010. PNPs are 54% more likely to be found in post-2008 clinical versus reference compounds. The majority of target classes show increased clinical compound NP character versus their reference compounds. Only 176 NP fragments appear in >1000 clinical compounds published since 2008, yet these make up on average 63% of the clinical compound's core scaffolds. There is untapped potential awaiting exploitation, by applying nature's building blocks─"natural intelligence"─to drug design.

Indexed as

Biological ProductsDrug DiscoverySmall Molecule LibrariesDrug DesignHumansBiological ProductsSmall Molecule Libraries

Identifiers

PMID38949112
PMCPMC11247505

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.