Evidence map›Paper›PMID 24755487›Full record

ArticleCancer biology & therapy2014

A novel synthetic 1,3-phenyl bis-thiourea compound targets microtubule polymerization to cause cancer cell death.

Jennifer C Shing, Jae Won Choi, Robert Chapman, Mark A Schroeder, Jann N Sarkaria, Abdul Fauq, Richard J Bram

Open access · bronzeAbstract read
In one paragraph

Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

6 citing papers in PubMed, 31 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 5 institutions in 1 country.

Jennifer C ShingDepartment of Molecular Pharmacology and Experimental Therapeutics; Mayo Clinic College of Medicine; Rochester, MN USA.
Jae Won ChoiDepartment of Pharmacology; Case Western Reserve University School of Medicine; Cleveland, OH USA.
Robert ChapmanDepartment of Chemistry; University of Georgia; Athens, GA USA.
Mark A SchroederDepartment of Radiation Oncology; Mayo Clinic College of Medicine; Rochester, MN USA.
Jann N SarkariaDepartment of Radiation Oncology; Mayo Clinic College of Medicine; Rochester, MN USA.
Abdul FauqDepartment of Chemistry; University of North Florida; Jacksonville, FL USA.
Richard J BramDepartment of Pediatric and Adolescent Medicine; Mayo Clinic College of Medicine; Rochester, MN USA; Department of Immunology; Mayo Clinic College of Medicine; Rochester, MN USA.
Mayo Clinic · USUniversity of Minnesota Rochester · USCase Western Reserve University · USPiedmont Athens Regional · USUniversity of North Florida · US

Funding

Targeted MV-CEA as a Potent Antitumor Agent against GBMP50CA108961 · NCI · MAYO CLINIC ROCHESTER · PI O'NEILL, BRIAN PATRICK · 2004 to 2015
$22.5M
Cyclophilin B as a therapeutic target in glioblastomaR01NS077555 · NINDS · MAYO CLINIC ROCHESTER · PI BRAM, RICHARD J · 2011 to 2015
$1.7M
NCI NIH HHS P50 CA108961NINDS NIH HHS R01 NS077555NINDS NIH HHS R01NS077555-01
6 · The paper itself

Abstract

Microtubules are essential cytoskeletal components with a central role in mitosis and have been particularly useful as a cancer chemotherapy target. We synthesized a small molecule derivative of a symmetrical 1,3-phenyl bis-thiourea, (1,1'-[1,3-phenylene]bis[3-(3,5-dimethylphenyl)thiourea], named "41J"), and identified a potent effect of the compound on cancer cell survival. 41J is cytotoxic to multiple cancer cell lines at nanomolar concentrations. Cell death occurred by apoptosis and was preceded by mitotic arrest in prometaphase. Prometaphase arrest induced by 41J treatment was accompanied by dissociation of cyclin B1 levels from the apparent mitotic stage and by major spindle abnormalities. Polymerization of purified tubulin in vitro was directly inhibited by 41J, suggesting that the compound works by directly interfering with microtubule function. Compound 41J arrested the growth of glioblastoma multiforme xenografts in nude mice at doses that were well-tolerated, demonstrating a relatively specific antitumor effect. Importantly, 41J overcame drug resistance due to β-tubulin mutation and P-glycoprotein overexpression. Compound 41J may serve as a useful new lead compound for anticancer therapy development.

Indexed as

AnimalsAntineoplastic AgentsApoptosisATP Binding Cassette Transporter, Subfamily B, Member 1Cell Cycle CheckpointsCell Line, TumorCentral Nervous System NeoplasmsCricetulusCyclin B1Drug Resistance, NeoplasmGlioblastomaHeterograftsHumansMice, NudeMicrotubulesPolymerization1,1'-(1,3-phenylene)bis(3-(3,5-dimethylphenyl)thiourea)Antineoplastic AgentsATP Binding Cassette Transporter, Subfamily B, Member 1Cyclin B1ThioureaTubulinchemotherapydrug resistancemicrotubulemitosisxenograft

Identifiers

PMID24755487
PMCPMC4100990
OpenAlexW2084721529

What OpenQuestion holds

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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.