Evidence map›Paper›PMID 33283450›Full record

ArticleChemMedChem2021

Systematic Assessment of Fragment Identification for Multitarget Drug Design.

Steffen Brunst, Jan S Kramer, Whitney Kilu, Jan Heering, Julius Pollinger, Kerstin Hiesinger, Sven George, Dieter Steinhilber, Daniel Merk, Ewgenij Proschak

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. 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.

Steffen BrunstInstitute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Str. 9, 60438, Frankfurt, Germany.
Jan S KramerInstitute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Str. 9, 60438, Frankfurt, Germany.
Whitney KiluInstitute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Str. 9, 60438, Frankfurt, Germany.
Jan HeeringFraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596, Frankfurt, Germany.
Julius PollingerInstitute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Str. 9, 60438, Frankfurt, Germany.
Kerstin HiesingerInstitute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Str. 9, 60438, Frankfurt, Germany.
Sven GeorgeInstitute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Str. 9, 60438, Frankfurt, Germany.
Dieter SteinhilberInstitute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Str. 9, 60438, Frankfurt, Germany.
Daniel MerkInstitute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Str. 9, 60438, Frankfurt, Germany.
Ewgenij ProschakInstitute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Str. 9, 60438, Frankfurt, Germany.ORCID 0000-0003-1961-1859

Funding

German Research Foundation DFGGerman Research Foundation PR1405/2-2German Research Foundation PR1405/4-1German Research Foundation SFB1039German Research Foundation Teilprojekt A02German Research Foundation Teilprojekt A07
6 · The paper itself

Abstract

Designed multitarget ligands are a popular approach to generating efficient and safe drugs, and fragment-based strategies have been postulated as a versatile avenue to discover multitarget ligand leads. To systematically probe the potential of fragment-based multiple ligand discovery, we have employed a large fragment library for comprehensive screening on five targets chosen from proteins for which multitarget ligands have been successfully developed previously (soluble epoxide hydrolase, leukotriene A4 hydrolase, 5-lipoxygenase, retinoid X receptor, farnesoid X receptor). Differential scanning fluorimetry served as primary screening method before fragments hitting at least two targets were validated in orthogonal assays. Thereby, we obtained valuable fragment leads with dual-target engagement for six out of ten target combinations. Our results demonstrate the applicability of fragment-based approaches to identify starting points for polypharmacological compound development with certain limitations.

Indexed as

Drug DesignArachidonate 5-LipoxygenaseDose-Response Relationship, DrugEnzyme InhibitorsEpoxide HydrolasesHumansMolecular StructureReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearRetinoid X ReceptorsStructure-Activity RelationshipArachidonate 5-LipoxygenaseEnzyme InhibitorsEpoxide Hydrolasesleukotriene A4 hydrolaseReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearRetinoid X Receptorsdifferential scanning fluorimetryfragment-based drug designmultitarget drugspolypharmacology

Identifiers

PMID33283450
PMCPMC8049054

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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.