Evidence map›Paper›PMID 28626832›Full record

ArticleACS omega2017

Fragment Binding to β-Secretase 1 without Catalytic Aspartate Interactions Identified via Orthogonal Screening Approaches.

Frederik J R Rombouts, Richard Alexander, Erna Cleiren, Alex De Groot, Michel Carpentier, Joyce Dijkmans, Katleen Fierens, Stefan Masure, Diederik Moechars, Martina Palomino-Schätzlein and 5 more

Abstract read
In one paragraph

Article in ACS omega, 2017. 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
–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

4 citing papers in PubMed.

  1. Review
  2. Article
  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

15 authors.

Frederik J R RomboutsNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Richard AlexanderDiscovery Sciences, Janssen Research & Development, 1400 McKean Road, Spring House, Pennsylvania 19477, United States.
Erna CleirenNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Alex De GrootNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Michel CarpentierNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Joyce DijkmansNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Katleen FierensNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Stefan MasureNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Diederik MoecharsNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Martina Palomino-SchätzleinStructural Biochemistry Laboratory, Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera, 3, 46012 Valencia, Spain.
Antonio Pineda-LucenaStructural Biochemistry Laboratory, Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera, 3, 46012 Valencia, Spain.
Andrés A TrabancoNeuroscience Medicinal Chemistry, Janssen Research & Development, C/ Jarama 75A, 45007 Toledo, Spain.
Daan Van GlabbeekNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Ann VosNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Gary TresadernNeuroscience Medicinal Chemistry, Discovery Sciences, and Neuroscience Biology, Janssen Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

An approach to identify β-secretase 1 (BACE1) fragment binders that do not interact with the catalytic aspartate dyad is presented. A ThermoFluor (thermal shift) and a fluorescence resonance energy transfer enzymatic screen on the soluble domain of BACE1, together with a surface plasmon resonance (SPR) screen on the soluble domain of BACE1 and a mutant of one catalytic Asp (D32N), were run in parallel. Fragments that were active in at least two of these assays were further confirmed using one-dimensional NMR (WaterLOGSY) and SPR binding competition studies with peptidic inhibitor OM99-2. Protein-observed NMR (two-dimensional

Identifiers

PMID28626832
PMCPMC5472370

What Socratic holds

Textmetadata
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.