Evidence map›Paper›PMID 24025110›Full record

ArticleTraffic (Copenhagen, Denmark)2013

Building a better dynasore: the dyngo compounds potently inhibit dynamin and endocytosis.

Adam McCluskey, James A Daniel, Gordana Hadzic, Ngoc Chau, Emma L Clayton, Anna Mariana, Ainslie Whiting, Nick N Gorgani, Jonathan Lloyd, Annie Quan and 18 more

Open access · hybridAbstract read
In one paragraph

Article in Traffic (Copenhagen, Denmark), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
178citing papers in PubMed, 1 pooled it
8.5field-weighted citation impact, top 2% 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

178 citing papers in PubMed, 1 synthesis or guideline pooled it, 339 citations in OpenAlex.

  1. Pooled it
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  14. Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026
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118 more citing papers are in PubMed but not listed here.

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

28 authors at 10 institutions in 4 countries.

Adam McCluskeyChemistry, Centre for Chemical Biology, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW, 2308, Australia.
James A Daniel
Gordana Hadzic
Ngoc Chau
Emma L Clayton
Anna Mariana
Ainslie Whiting
Nick N Gorgani
Jonathan Lloyd
Annie Quan
Lia Moshkanbaryans
Sai Krishnan
Swetha Perera
Megan Chircop
Lisa von Kleist
Andrew B McGeachie
Mark T Howes
Robert G Parton
Michael Campbell
Jennette A Sakoff
Xuefeng Wang
Jian-Yuan Sun
Mark J Robertson
Fiona M Deane
Tam H Nguyen
Frederic A Meunier
Michael A Cousin
Phillip J Robinson
University of Sydney · AUChildren's Medical Research Institute · AUUniversity of Newcastle Australia · AUUniversity of Queensland · AUChinese Academy of Sciences · CNUniversity of Edinburgh · GBCalvary Mater Newcastle Hospital · AUFreie Universität Berlin · DEMonash University · AUNeuroscience Research Australia · AU

Funding

Wellcome TrustWellcome Trust 084277
6 · The paper itself

Abstract

Dynamin GTPase activity increases when it oligomerizes either into helices in the presence of lipid templates or into rings in the presence of SH3 domain proteins. Dynasore is a dynamin inhibitor of moderate potency (IC₅₀ ~ 15 μM in vitro). We show that dynasore binds stoichiometrically to detergents used for in vitro drug screening, drastically reducing its potency (IC₅₀ = 479 μM) and research tool utility. We synthesized a focused set of dihydroxyl and trihydroxyl dynasore analogs called the Dyngo™ compounds, five of which had improved potency, reduced detergent binding and reduced cytotoxicity, conferred by changes in the position and/or number of hydroxyl substituents. The Dyngo compound 4a was the most potent compound, exhibiting a 37-fold improvement in potency over dynasore for liposome-stimulated helical dynamin activity. In contrast, while dynasore about equally inhibited dynamin assembled in its helical or ring states, 4a and 6a exhibited >36-fold reduced activity against rings, suggesting that they can discriminate between helical or ring oligomerization states. 4a and 6a inhibited dynamin-dependent endocytosis of transferrin in multiple cell types (IC₅₀ of 5.7 and 5.8 μM, respectively), at least sixfold more potently than dynasore, but had no effect on dynamin-independent endocytosis of cholera toxin. 4a also reduced synaptic vesicle endocytosis and activity-dependent bulk endocytosis in cultured neurons and synaptosomes. Overall, 4a and 6a are improved and versatile helical dynamin and endocytosis inhibitors in terms of potency, non-specific binding and cytotoxicity. The data further suggest that the ring oligomerization state of dynamin is not required for clathrin-mediated endocytosis.

Indexed as

AnimalsCell Line, TumorCells, CulturedCholera ToxinDose-Response Relationship, DrugDrug DiscoveryDynaminsEndocytosisHigh-Throughput Screening AssaysHumansHydrazonesNaphtholsNeuronsProtein BindingProtein TransportRatsCholera ToxinDynaminsdyngo-4aHydrazonesN'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazideNaphtholsTransferrinsbulk endocytosisdrug discoverydynaminhigh-throughput screeningsmall-molecule inhibitorssynaptic vesicle endocytosis

Identifiers

PMID24025110
PMCPMC4138991
OpenAlexW1526128150

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.