Evidence map›Paper›PMID 34849907›Full record

ArticleGenetics2021

Discovery of new vascular disrupting agents based on evolutionarily conserved drug action, pesticide resistance mutations, and humanized yeast.

Riddhiman K Garge, Hye Ji Cha, Chanjae Lee, Jimmy D Gollihar, Aashiq H Kachroo, John B Wallingford, Edward M Marcotte

Open access · bronzeAbstract read
In one paragraph

Article in Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

7 authors at 4 institutions in 2 countries.

Riddhiman K GargeDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.ORCID 0000-0002-6774-0172
Hye Ji ChaDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Chanjae LeeDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Jimmy D GolliharDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Aashiq H KachrooThe Department of Biology, Centre for Applied Synthetic Biology, Concordia University, Montreal, QC H4B 1R6, Canada.ORCID 0000-0001-9770-778X
John B WallingfordDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Edward M MarcotteDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.ORCID 0000-0001-8808-180X
The University of Texas at Austin · USBoston Children's Hospital · USConcordia University · CADEVCOM Army Research Laboratory · US

Funding

Proteomics and model organism humanization to decode human geneticsR35GM122480 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI EDWARD M MARCOTTE · 2017 to 2026
$5.4M
Molecular and cell biological basis of convergent extensionR01HD099191 · NICHD · UNIVERSITY OF TEXAS AT AUSTIN · PI John B Wallingford · 2020 to 2026
$2.7M
National Institute of Child Health and Human Development R01HD099191NICHD NIH HHS R01 HD099191NIGMS NIH HHS R35 GM122480NIH HHS R35 GM122480
6 · The paper itself

Abstract

Thiabendazole (TBZ) is an FDA-approved benzimidazole widely used for its antifungal and antihelminthic properties. We showed previously that TBZ is also a potent vascular disrupting agent and inhibits angiogenesis at the tissue level by dissociating vascular endothelial cells in newly formed blood vessels. Here, we uncover TBZ's molecular target and mechanism of action. Using human cell culture, molecular modeling, and humanized yeast, we find that TBZ selectively targets only 1 of 9 human β-tubulin isotypes (TUBB8) to specifically disrupt endothelial cell microtubules. By leveraging epidemiological pesticide resistance data and mining chemical features of commercially used benzimidazoles, we discover that a broader class of benzimidazole compounds, in extensive use for 50 years, also potently disrupt immature blood vessels and inhibit angiogenesis. Thus, besides identifying the molecular mechanism of benzimidazole-mediated vascular disruption, this study presents evidence relevant to the widespread use of these compounds while offering potential new clinical applications.

Indexed as

BenzimidazolesThiabendazoleTubulinAngiogenesis InhibitorsEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsMicrotubulesMutationPesticidesSaccharomyces cerevisiaeAngiogenesis InhibitorsBenzimidazolesPesticidesThiabendazoleTubulinangiogenesisepidemiologyevolutionhumanized yeastphenologssystems biologyvascular disrupting agents

Identifiers

PMID34849907
PMCPMC8633126
OpenAlexW3180612371

What OpenQuestion 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 OpenQuestion graph.