Evidence map›Paper›PMID 25047940›Full record

ArticleBioorganic & medicinal chemistry2014

Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione derivatives as eEF-2K inhibitors.

Ramakrishna Edupuganti, Qiantao Wang, Clint D J Tavares, Catrina A Chitjian, James L Bachman, Pengyu Ren, Eric V Anslyn, Kevin N Dalby

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 76 citations in OpenAlex.

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  17. 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

8 authors at 1 institution in 1 country.

Ramakrishna EdupugantiDivision of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, TX 78712, USA; Department of Chemistry, The University of Texas at Austin, TX 78712, USA.
Qiantao WangDivision of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, TX 78712, USA; Department of Biomedical Engineering, Cockrell School of Engineering, College of Engineering, The University of Texas at Austin, TX 78712, USA.
Clint D J TavaresGraduate Program in Cell and Molecular Biology, The University of Texas at Austin, TX 78712, USA.
Catrina A ChitjianGraduate Program in Cell and Molecular Biology, The University of Texas at Austin, TX 78712, USA.
James L BachmanDepartment of Chemistry, The University of Texas at Austin, TX 78712, USA.
Pengyu RenDepartment of Biomedical Engineering, Cockrell School of Engineering, College of Engineering, The University of Texas at Austin, TX 78712, USA.
Eric V AnslynDepartment of Chemistry, The University of Texas at Austin, TX 78712, USA. Electronic address: anslyn@austin.utexas.edu.
Kevin N DalbyDivision of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, TX 78712, USA; Graduate Program in Cell and Molecular Biology, The University of Texas at Austin, TX 78712, USA. Electronic address: dalby@austin.utexas.edu.
The University of Texas at Austin · US

Funding

Mechanism and Specificity of MAP KinasesR01GM059802 · NIGMS · UNIVERSITY OF TEXAS AUSTIN · PI DALBY, KEVIN N · 2001 to 2011
$2.3M
NIGMS NIH HHS GM59802NIGMS NIH HHS R01 GM059802
6 · The paper itself

Abstract

A small molecule library of pyrido[2,3-d]pyrimidine-2,4-dione derivatives 6-16 was synthesized from 6-amino-1,3-disubstituted uracils 18, characterized, and screened for inhibitory activity against eukaryotic elongation factor-2 kinase (eEF-2K). To understand the binding pocket of eEF-2K, structural modifications of the pyrido[2,3-d]pyrimidine were made at three regions (R(1), R(2), and R(3)). A homology model of eEF-2K was created, and compound 6 (A-484954, Abbott laboratories) was docked in the catalytic domain of eEF-2K. Compounds 6 (IC50=420nM) and 9 (IC50=930nM) are found to be better molecules in this preliminary series of pyrido[2,3-d]pyrimidine analogs. eEF-2K activity in MDA-MB-231 breast cancer cells is significantly reduced by compound 6, to a lesser extent by compound 9, and is unaffected by compound 12. Similar inhibitory results are observed when eEF-2K activity is stimulated by 2-deoxy-d-glucose (2-DOG) treatment, suggesting that compounds 6 and 9 are able to inhibit AMPK-mediated activation of eEF-2K to a notable extent. The results of this work will shed light on the further design and optimization of novel pyrido[2,3-d]pyrimidine analogs as eEF-2K inhibitors.

Indexed as

Dose-Response Relationship, DrugElongation Factor 2 KinaseHumansMolecular StructureProtein Kinase InhibitorsPyridinesPyrimidinonesRecombinant ProteinsStructure-Activity RelationshipTumor Cells, CulturedEEF2K protein, humanElongation Factor 2 KinaseProtein Kinase InhibitorsPyridinesPyrimidinonesRecombinant ProteinseEF-2K inhibitorHomology modelingKinase inhibitorPyrido[2,3-d]pyrimidine-2,4-dioneUracil

Identifiers

PMID25047940
PMCPMC6473179
OpenAlexW2000602679

What OpenQuestion holds

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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.