Evidence map›Paper›PMID 37090247›Full record

ArticleFrontiers in chemistry2023

From PERK to RIPK1: Design, synthesis and evaluation of novel potent and selective necroptosis inhibitors.

Camilla Scarpellini, Sophie Valembois, Kenneth Goossens, Mike Vadi, Caroline Lanthier, Greta Klejborowska, Pieter Van Der Veken, Hans De Winter, Mathieu J M Bertrand, Koen Augustyns

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

Article in Frontiers in chemistry, 2023. 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
0.5field-weighted citation impact, top 34% 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

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  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 at 3 institutions in 1 country.

Camilla ScarpelliniLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Sophie ValemboisLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Kenneth GoossensLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Mike VadiVlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Ghent, Belgium.
Caroline LanthierLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Greta KlejborowskaLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Pieter Van Der VekenLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Hans De WinterLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
Mathieu J M BertrandVlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Ghent, Belgium.
Koen AugustynsLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
University of Antwerp · BEGhent University · BEVlaams Instituut voor Biotechnologie · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Receptor-Interacting serine/threonine-Protein Kinase 1 (RIPK1) emerged as an important driver of inflammation and, consequently, inflammatory pathologies. The enzymatic activity of RIPK1 is known to indirectly promote inflammation by triggering cell death, in the form of apoptosis, necroptosis and pyroptosis. Small molecule Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitors have therefore recently entered clinical trials for the treatment of a subset of inflammatory pathologies. We previously identified GSK2656157 (GSK'157), a supposedly specific inhibitor of protein kinase R (PKR)-like ER kinase (PERK), as a much more potent type II Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitor. We now performed further structural optimisation on the GSK'157 scaffold in order to develop a novel class of more selective Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitors. Based on a structure-activity relationship (SAR) reported in the literature, we anticipated that introducing a substituent on the

Indexed as

inflammationnecroptosisPERK (PKR-like endoplasmic reticulum kinase)regulated cell deathRIPK1 inhibitortype II kinase inhibitor

Identifiers

PMID37090247
PMCPMC10119423
OpenAlexW4362700826

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.