Evidence map›Paper›PMID 35215359›Full record

ArticlePharmaceuticals (Basel, Switzerland)2022

From the North Sea to Drug Repurposing, the Antiseizure Activity of Halimide and Plinabulin.

Daniëlle Copmans, Sara Kildgaard, Emma Roux, Michèle Partoens, Gert Steurs, Xinhui Wang, Wim M De Borggraeve, Camila V Esguerra, Alexander D Crawford, Thomas O Larsen and 1 more

Open access · goldAbstract read
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

5 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
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  4. Review
  5. Review
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

11 authors at 2 institutions in 2 countries.

Daniëlle CopmansLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49 box 824, 3000 Leuven, Belgium.ORCID 0000-0002-9804-8410
Sara KildgaardDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, Building 221, 2800 Kgs. Lyngby, Denmark.
Emma RouxLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49 box 824, 3000 Leuven, Belgium.ORCID 0000-0003-2629-6316
Michèle PartoensLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49 box 824, 3000 Leuven, Belgium.
Gert SteursMolecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200f box 2404, 3001 Leuven, Belgium.ORCID 0000-0002-9779-7743
Xinhui WangDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, Building 221, 2800 Kgs. Lyngby, Denmark.ORCID 0000-0003-0472-413X
Wim M De BorggraeveMolecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200f box 2404, 3001 Leuven, Belgium.ORCID 0000-0001-7813-6192
Camila V EsguerraLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49 box 824, 3000 Leuven, Belgium.
Alexander D CrawfordLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49 box 824, 3000 Leuven, Belgium.
Thomas O LarsenDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, Building 221, 2800 Kgs. Lyngby, Denmark.
Peter A M de WitteLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49 box 824, 3000 Leuven, Belgium.ORCID 0000-0002-9989-9567
KU Leuven · BETechnical University of Denmark · DK

Funding

EU Seventh Framework Programme 312184Fund for Scientific Research Flanders 1S84418NFund for Scientific Research Flanders 1SC3119N|1SC3121NKU Leuven C32/17/044
6 · The paper itself

Abstract

PharmaSea performed large-scale in vivo screening of marine natural product (MNP) extracts, using zebrafish embryos and larvae, to identify compounds with the potential to treat epilepsy. In this study, we report the discovery of two new antiseizure compounds, the 2,5-diketopiperazine halimide and its semi-synthetic analogue, plinabulin. Interestingly, these are both known microtubule destabilizing agents, and plinabulin could have the potential for drug repurposing, as it is already in clinical trials for the prevention of chemotherapy-induced neutropenia and treatment of non-small cell lung cancer. Both halimide and plinabulin were found to have antiseizure activity in the larval zebrafish pentylenetetrazole (PTZ) seizure model via automated locomotor analysis and non-invasive local field potential recordings. The efficacy of plinabulin was further characterized in animal models of drug-resistant seizures, i.e., the larval zebrafish ethyl ketopentenoate (EKP) seizure model and the mouse 6 Hz psychomotor seizure model. Plinabulin was observed to be highly effective against EKP-induced seizures, on the behavioral and electrophysiological level, and showed activity in the mouse model. These data suggest that plinabulin could be of interest for the treatment of drug-resistant seizures. Finally, the investigation of two functional analogues, colchicine and indibulin, which were observed to be inactive against EKP-induced seizures, suggests that microtubule depolymerization does not underpin plinabulin's antiseizure action.

Indexed as

drug discoveryepilepsyhalimidemarine natural productsplinabulinzebrafish

Identifiers

PMID35215359
PMCPMC8878679
OpenAlexW4213059463

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.