Evidence map›Paper›PMID 31908412›Full record

ArticleDrug design, development and therapy2019

Small-Molecule Intervention At The Dimerization Interface Of Survivin By Novel Rigidized Scaffolds.

Tamer M Ibrahim, Christoph Ernst, Andreas Lange, Susanne Hennig, Frank M Boeckler

Open access · goldAbstract read
In one paragraph

Article in Drug design, development and therapy, 2019. 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
0.3field-weighted citation impact, top 42% 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, 12 citations in OpenAlex.

  1. Review
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  3. Review
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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

5 authors at 2 institutions in 2 countries.

Tamer M IbrahimLaboratory for Molecular Design and Pharmaceutical Biophysics, Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.ORCID 0000-0003-1016-8950
Christoph ErnstLaboratory for Molecular Design and Pharmaceutical Biophysics, Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Andreas LangeLaboratory for Molecular Design and Pharmaceutical Biophysics, Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.ORCID 0000-0003-3871-1986
Susanne HennigLaboratory for Molecular Design and Pharmaceutical Biophysics, Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
Frank M BoecklerLaboratory for Molecular Design and Pharmaceutical Biophysics, Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.ORCID 0000-0001-8738-6716
University of Tübingen · DEKafrelsheikh University · EG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSurvivin is a nodal protein involved in several cellular pathways. It is a member of the IAP family and an integral component of the chromosomal passenger complex, where it binds to borealin and INCENP through its dimerization interface. By targeting survivin with a small molecule at its dimerization interface, inhibition of the proliferation of cancer cells has been suggested. With Abbott 8, a small-molecule dimerization inhibitor has been recently reported. The structure-activity relationship of this series of inhibitors implied that the middle pyridin-2(1

methodsBased on the synthetic strategy of Abbott 8 using multicomponent reactions, we synthesized a series of small molecules bearing a novel rigidized core scaffold. This rigidization strategy was accomplished by integrating the pyridin-2(1

resultsBinding of these rigidized scaffolds to the recombinant L54M mutant of survivin was evaluated, revealing affinities in the low micromolar range.

conclusionThis easily accessible, new class of survivin-dimerization modulators is an interesting starting point for further lead optimization.

Indexed as

Molecular Dynamics SimulationProtein MultimerizationHumansMolecular StructureMutationPyridonesRecombinant ProteinsSmall Molecule LibrariesSurvivinPyridonesRecombinant ProteinsSmall Molecule LibrariesSurvivinmolecular dynamics and designone-pot synthesispyridin-2(1H)-one derivativessurvivin-dimerization modulators

Identifiers

PMID31908412
PMCPMC6927794
OpenAlexW2996102926

What OpenQuestion holds

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LicenceCC BY-NC
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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.