Evidence map›Paper›PMID 38071198›Full record

ArticleNature communications2023

Harnessing PROTAC technology to combat stress hormone receptor activation.

Mahshid Gazorpak, Karina M Hugentobler, Dominique Paul, Pierre-Luc Germain, Miriam Kretschmer, Iryna Ivanova, Selina Frei, Kei Mathis, Remo Rudolf, Sergio Mompart Barrenechea and 11 more

Abstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Light-controlled disruption of cancer cell dormancy via photoswitchable stress hormone receptor degraders.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  9. Glucocorticoids Rapidly Modulate CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  10. Review
  11. Article
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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.

Mahshid Gazorpak *Laboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.ORCID 0009-0008-0454-2313
Karina M Hugentobler *Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093, Zürich, Switzerland.ORCID 0000-0002-7557-6675
Dominique PaulLab of Statistical Bioinformatics, University of Zürich, 8057, Zürich, Switzerland.
Pierre-Luc GermainLaboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.ORCID 0000-0003-3418-4218
Miriam KretschmerLaboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.ORCID 0000-0002-9340-309X
Iryna IvanovaLaboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.ORCID 0009-0004-8870-4279
Selina FreiLaboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.
Kei MathisLaboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.ORCID 0009-0009-8348-6803
Remo RudolfLaboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.ORCID 0009-0001-2075-6548
Sergio Mompart BarrenecheaLaboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.ORCID 0009-0001-6987-6241
Vincent FischerLaboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.ORCID 0009-0007-7332-6182
Xiaohan XueBio Engineering Laboratory, Department of Biosystems Science and Engineering, ETH Zürich, 4056, Basel, Switzerland.ORCID 0000-0001-5398-2368
Aleksandra L PtaszekChristian Doppler Laboratory for High-Content Structural Biology and Biotechnology, Max Perutz Laboratories, Department of Structural and Computational Biology, University of Vienna, Campus Vienna Biocenter 5, 1030, Vienna, Austria.ORCID 0000-0002-9111-995X
Julian HolzingerChristian Doppler Laboratory for High-Content Structural Biology and Biotechnology, Max Perutz Laboratories, Department of Structural and Computational Biology, University of Vienna, Campus Vienna Biocenter 5, 1030, Vienna, Austria.ORCID 0000-0002-0530-8413
Mattia PriviteraLaboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland.ORCID 0000-0002-5660-5901
Andreas HierlemannBio Engineering Laboratory, Department of Biosystems Science and Engineering, ETH Zürich, 4056, Basel, Switzerland.ORCID 0000-0002-3838-2468
Onno C MeijerDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, 2300, RA, Leiden, the Netherlands.ORCID 0000-0002-8394-6859
Robert KonratDepartment of Structural and Computational Biology, University of Vienna, Campus Vienna Biocenter 5, 1030, Vienna, Austria.
Erick M CarreiraLaboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093, Zürich, Switzerland.
Johannes BohacekNeuroscience Center Zürich, ETH Zürich and University of Zürich, 8057, Zürich, Switzerland.ORCID 0000-0002-8442-653X
Katharina GappLaboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, 8057, Zürich, Switzerland. katharina.gapp@hest.ethz.ch.ORCID 0000-0002-9622-1478

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 310030_204372Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) PR00P3_201543
6 · The paper itself

Abstract

Counteracting the overactivation of glucocorticoid receptors (GR) is an important therapeutic goal in stress-related psychiatry and beyond. The only clinically approved GR antagonist lacks selectivity and induces unwanted side effects. To complement existing tools of small-molecule-based inhibitors, we present a highly potent, catalytically-driven GR degrader, KH-103, based on proteolysis-targeting chimera technology. This selective degrader enables immediate and reversible GR depletion that is independent of genetic manipulation and circumvents transcriptional adaptations to inhibition. KH-103 achieves passive inhibition, preventing agonistic induction of gene expression, and significantly averts the GR's genomic effects compared to two currently available inhibitors. Application in primary-neuron cultures revealed the dependency of a glucocorticoid-induced increase in spontaneous calcium activity on GR. Finally, we present a proof of concept for application in vivo. KH-103 opens opportunities for a more lucid interpretation of GR functions with translational potential.

Indexed as

GlucocorticoidsReceptors, GlucocorticoidGlucocorticoidsReceptors, Glucocorticoid

Identifiers

PMID38071198
PMCPMC10710461

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.