Evidence map›Paper›PMID 33180487›Full record

ArticleJournal of medicinal chemistry2020

A Multipronged Approach Establishes Covalent Modification of β-Tubulin as the Mode of Action of Benzamide Anti-cancer Toxins.

Juan Manuel Povedano, Rameshu Rallabandi, Xin Bai, Xuecheng Ye, Joel Liou, Hong Chen, Jiwoong Kim, Yang Xie, Bruce Posner, Luke Rice and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-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

8 citing papers in PubMed, 9 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

12 authors at 1 institution in 1 country.

Juan Manuel PovedanoDepartment of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.ORCID 0000-0002-8384-6540
Rameshu RallabandiDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Xin BaiDepartment of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Xuecheng YeDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Joel LiouDepartment of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Hong ChenDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Jiwoong KimQuantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Yang XieQuantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Bruce PosnerDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Luke RiceDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Jef K De BrabanderDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.ORCID 0000-0001-8816-5798
David G McFaddenDepartment of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.ORCID 0000-0001-8466-2199
The University of Texas Southwestern Medical Center · US

Funding

Targeting EWSR1-FLI1 through Functional, Structural and Chemical ApproachesU54CA231649 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI AMATRUDA, JAMES F, MCFADDEN, DAVID GLENN · 2019 to 2019
$10.0M
CONFORMATION & RECOGNITION IN MICROTUBLE DYNAMICSR01GM098543 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI RICE, LUKE W · 2011 to 2023
$4.2M
NCI NIH HHS U54 CA231649NIGMS NIH HHS R01 GM098543
6 · The paper itself

Abstract

A phenotypic high-throughput screen identified a benzamide small molecule with activity against small cell lung cancer cells. A "clickable" benzamide probe was designed that irreversibly bound a single 50 kDa cellular protein, identified by mass spectrometry as β-tubulin. Moreover, the anti-cancer potency of a series of benzamide analogs strongly correlated with probe competition, indicating that β-tubulin was the functional target. Additional evidence suggested that benzamides covalently modified Cys239 within the colchicine binding site. Consistent with this mechanism, benzamides impaired growth of microtubules formed with β-tubulin harboring Cys239, but not β

Indexed as

Antineoplastic AgentsBenzamidesBinding SitesColchicineHumansLung NeoplasmsMicrotubulesProtein ConformationSmall Cell Lung CarcinomaStructure-Activity RelationshipTubulinTubulin ModulatorsAntineoplastic AgentsBenzamidesColchicineTubulinTubulin Modulators

Identifiers

PMID33180487
PMCPMC7707623
OpenAlexW3105358807

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.