Evidence map›Paper›PMID 36768348›Full record

ArticleInternational journal of molecular sciences2023

Inhibition of Neutral Sphingomyelinase 2 by Novel Small Molecule Inhibitors Results in Decreased Release of Extracellular Vesicles by Vascular Smooth Muscle Cells and Attenuated Calcification.

Angelina Pavlic, Hessel Poelman, Grzegorz Wasilewski, Kanin Wichapong, Petra Lux, Cecile Maassen, Esther Lutgens, Leon J Schurgers, Chris P Reutelingsperger, Gerry A F Nicolaes

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

8 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Structural bioinformatics for rational drug design.Research and practice in thrombosis and haemostasis · 2025
    Article
  5. Article
  6. Review
  7. Review
  8. 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 2 institutions in 3 countries.

Angelina PavlicDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
Hessel PoelmanDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
Grzegorz WasilewskiDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
Kanin WichapongDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-9678-7084
Petra LuxDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0001-7269-4011
Cecile MaassenDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
Esther LutgensAmsterdam UMC, University of Amsterdam, Medical Biochemistry, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Leon J SchurgersDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0001-7867-6957
Chris P ReutelingspergerDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-2334-9403
Gerry A F NicolaesDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-2482-0412
Maastricht University · NLMayo Clinic · US

Funding

HORIZON EUROPE Marie Sklodowska-Curie Actions 675111
6 · The paper itself

Abstract

Vascular calcification (VC) is an important contributor and prognostic factor in the pathogenesis of cardiovascular diseases. VC is an active process mediated by the release of extracellular vesicles by vascular smooth muscle cells (VSMCs), and the enzyme neutral sphingomyelinase 2 (nSMase2 or SMPD3) plays a key role. Upon activation, the enzyme catalyzes the hydrolysis of sphingomyelin, thereby generating ceramide and phosphocholine. This conversion mediates the release of exosomes, a type of extracellular vesicles (EVs), which ultimately forms the nidus for VC. nSMase2 therefore represents a drug target, the inhibition of which is thought to prevent or halt VC progression. In search of novel druglike small molecule inhibitors of nSMase2, we have used virtual ligand screening to identify potential ligands. From an in-silico collection of 48,6844 small druglike molecules, we selected 996 compounds after application of an in-house multi-step procedure combining different filtering and docking procedures. Selected compounds were functionally tested in vitro; from this, we identified 52 individual hit molecules that inhibited nSMase2 activity by more than 20% at a concentration of 150 µM. Further analysis showed that five compounds presented with IC

Indexed as

ExosomesMuscle, Smooth, VascularVascular CalcificationExtracellular VesiclesHumansSphingomyelin PhosphodiesteraseSMPD3 protein, humanSphingomyelin Phosphodiesterasedrug discoveryextracellular vesiclesnSMase2small moleculesSMPD3vascular calcificationvirtual ligand screening

Identifiers

PMID36768348
PMCPMC9916533
OpenAlexW4317625909

What Socratic 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 Socratic graph.