Evidence map›Paper›PMID 37708384›Full record

ArticleJournal of medicinal chemistry2023

Expanding the Structural Diversity at the Phenylene Core of Ligands for the von Hippel-Lindau E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia-Inducible Factor-1α Stabilizers.

Lan Phuong Vu, Claudia J Diehl, Ryan Casement, Adam G Bond, Christian Steinebach, Nika Strašek, Aleša Bricelj, Andrej Perdih, Gregor Schnakenburg, Izidor Sosič and 2 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

2 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. 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

12 authors at 3 institutions in 3 countries.

Lan Phuong VuPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
Claudia J DiehlCentre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, 1 James Lindsay Place, Dundee, Scotland DD1 5JJ, U.K.ORCID 0000-0001-5486-1453
Ryan CasementCentre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, 1 James Lindsay Place, Dundee, Scotland DD1 5JJ, U.K.
Adam G BondCentre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, 1 James Lindsay Place, Dundee, Scotland DD1 5JJ, U.K.ORCID 0000-0002-1271-1032
Christian SteinebachPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.ORCID 0000-0001-5638-1955
Nika StrašekFaculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.ORCID 0009-0008-8149-970X
Aleša BriceljFaculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
Andrej PerdihFaculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.ORCID 0000-0002-6645-9231
Gregor SchnakenburgInstitute of Inorganic Chemistry, University of Bonn, Gerhard-Domagk-Straße 1, D-53121 Bonn, Germany.
Izidor SosičFaculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.ORCID 0000-0002-3370-4587
Alessio CiulliCentre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, 1 James Lindsay Place, Dundee, Scotland DD1 5JJ, U.K.ORCID 0000-0002-8654-1670
Michael GütschowPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.ORCID 0000-0002-9376-7897
University of Bonn · DEUniversity of Dundee · GBUniversity of Ljubljana · SI

Funding

Biotechnology and Biological Sciences Research Council BB/M010996/1Wellcome TrustWellcome Trust 094090/Z/10/ZWellcome Trust 100476/Z/12/Z
6 · The paper itself

Abstract

Hypoxia-inducible factor-1α (HIF-1α) constitutes the principal mediator of cellular adaptation to hypoxia in humans. The HIF-1α protein level and activity are tightly regulated by the ubiquitin E3 ligase von Hippel-Lindau (VHL). Here, we performed a structure-guided and bioactivity-driven design of new VHL inhibitors. Our iterative and combinatorial strategy focused on chemical variability at the phenylene unit and encompassed further points of diversity. The exploitation of tailored phenylene fragments and the stereoselective installation of the benzylic methyl group provided potent VHL ligands. Three high-resolution structures of VHL-ligand complexes were determined, and bioactive conformations of these ligands were explored. The most potent inhibitor (

Indexed as

Ubiquitin-Protein LigasesVon Hippel-Lindau Tumor Suppressor ProteinHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitLigandsUbiquitinHypoxia-Inducible Factor 1, alpha SubunitLigandsUbiquitinUbiquitin-Protein LigasesVon Hippel-Lindau Tumor Suppressor Protein

Identifiers

PMID37708384
PMCPMC10544018
OpenAlexW4386734858

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.