Evidence map›Paper›PMID 31757667›Full record

ArticleBioorganic & medicinal chemistry letters2020

Novel compounds that reverse the disease phenotype in Type 2 Gaucher disease patient-derived cells.

Wayne Childers, Rong Fan, Rogelio Martinez, Dennis J Colussi, Edward Melenski, Yuxiao Liu, John Gordon, Magid Abou-Gharbia, Marlene A Jacobson

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

Article in Bioorganic & medicinal chemistry letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. The Resurrection of Phenotypic Drug Discovery.ACS medicinal chemistry letters · 2020
    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

9 authors at 1 institution in 1 country.

Wayne ChildersMoulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA. Electronic address: wayne.childers@temple.edu.
Rong FanMoulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Rogelio MartinezMoulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Dennis J ColussiMoulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Edward MelenskiMoulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Yuxiao LiuMoulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
John GordonMoulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Magid Abou-GharbiaMoulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Marlene A JacobsonMoulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA. Electronic address: marlene.jacobson@temple.edu.
Temple University · US

Funding

FDSS uCell Kinetic Plate ReaderS10OD018195 · OD · TEMPLE UNIV OF THE COMMONWEALTH · PI JACOBSON, MARLENE A · 2014 to 2014
$267k
NIH HHS S10 OD018195
6 · The paper itself

Abstract

Gaucher disease (GD) results from inherited mutations in the lysosomal enzyme β-glucocerobrosidase (GCase). Currently available treatment options for Type 1 GD are not efficacious for treating neuronopathic Type 2 and 3 GD due to their inability to cross the blood-brain barrier. In an effort to identify small molecules which could be optimized for CNS penetration we identified tamoxifen from a high throughput phenotypic screen on Type 2 GD patient-derived fibroblasts which reversed the disease phenotype. Structure activity studies around this scaffold led to novel molecules that displayed improved potency, efficacy and reduced estrogenic/antiestrogenic activity compared to the original hits. Here we present the design, synthesis and structure activity relationships that led to the lead molecule Compound 31.

Indexed as

Cells, CulturedFibroblastsGaucher DiseaseGlucosylceramidaseHumansInhibitory Concentration 50LysosomesPhenotypeSmall Molecule LibrariesStructure-Activity RelationshipTamoxifenGlucosylceramidaseSmall Molecule LibrariesTamoxifenDiphenylethanonoGaucher diseaseLysosomal storage diseaseNeuronopathicPhenotypic screening

Identifiers

PMID31757667
PMCPMC7569734
OpenAlexW2986319260

What OpenQuestion holds

Textmetadata
LicenceTDM
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.