Evidence map›Paper›PMID 29349898›Full record

ArticleChemMedChem2018

Helenalin Analogues Targeting NF-κB p65: Thiol Reactivity and Cellular Potency Studies of Varied Electrophiles.

John C Widen, Aaron M Kempema, Jordan W Baur, Hannah M Skopec, Jacob T Edwards, Tenley J Brown, Dennis A Brown, Frederick A Meece, Daniel A Harki

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

12 citing papers in PubMed, 23 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

9 authors at 1 institution in 1 country.

John C WidenDepartment of Medicinal Chemistry, University of Minnesota, 2231 6th Street S.E., Minneapolis, MN, 55455, USA.
Aaron M KempemaDepartment of Medicinal Chemistry, University of Minnesota, 2231 6th Street S.E., Minneapolis, MN, 55455, USA.
Jordan W BaurDepartment of Medicinal Chemistry, University of Minnesota, 2231 6th Street S.E., Minneapolis, MN, 55455, USA.
Hannah M SkopecDepartment of Medicinal Chemistry, University of Minnesota, 2231 6th Street S.E., Minneapolis, MN, 55455, USA.
Jacob T EdwardsDepartment of Medicinal Chemistry, University of Minnesota, 2231 6th Street S.E., Minneapolis, MN, 55455, USA.
Tenley J BrownDepartment of Medicinal Chemistry, University of Minnesota, 2231 6th Street S.E., Minneapolis, MN, 55455, USA.
Dennis A BrownDepartment of Medicinal Chemistry, University of Minnesota, 2231 6th Street S.E., Minneapolis, MN, 55455, USA.
Frederick A MeeceDepartment of Medicinal Chemistry, University of Minnesota, 2231 6th Street S.E., Minneapolis, MN, 55455, USA.
Daniel A HarkiDepartment of Medicinal Chemistry, University of Minnesota, 2231 6th Street S.E., Minneapolis, MN, 55455, USA.ORCID 0000-0001-5950-931X
University of Minnesota · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
LTQ Orbitrap XL Mass SpectrometerS10RR024618 · NCRR · UNIVERSITY OF MINNESOTA · PI VILLALTA, PETER WILLIAM · 2009 to 2009
$500k
CHEMOPROTEOMICS PROFILING OF PARTHENOLIDE IN HUMAN GLIOBLASTOMAR21CA194661 · NCI · UNIVERSITY OF MINNESOTA · PI HARKI, DANIEL A · 2015 to 2016
$355k
NCI NIH HHS P30 CA077598NCI NIH HHS R21 CA194661NCRR NIH HHS S10 RR024618
6 · The paper itself

Abstract

Helenalin is a pseudoguaianolide natural product that targets Cys38 within the DNA binding domain of NF-κB transcription factor p65 (RelA). Helenalin contains two Michael acceptors that covalently modify cysteines: a α-methylene-γ-butyrolactone and a cyclopentenone. We recently reported two simplified helenalin analogues that mimic the biological activity of helenalin and contain both electrophilic moieties. To determine the individual contributions of the Michael acceptors toward NF-κB inhibition, we synthesized a small library of helenalin-based analogues containing various combinations of α-methylene-γ-butyrolactones and cyclopentenones. The kinetics of thiol addition to a subset of the analogues was measured to determine the relative thiol reactivities of the embedded electrophiles. Additionally, the cellular NF-κB inhibitory activities of the analogues were determined to elucidate the contributions of each Michael acceptor to biological potency. Our studies suggest the α-methylene-γ-butyrolactone contributes most significantly to the NF-κB inhibition of our simplified helenalin analogues.

Indexed as

A549 CellsCysteineHumansKineticsSesquiterpenesSesquiterpenes, GuaianeSulfhydryl CompoundsTranscription Factor RelACysteinehelenalinSesquiterpenesSesquiterpenes, GuaianeSulfhydryl CompoundsTranscription Factor RelAbis-electrophilescysteine reactivehelenalinMichael acceptorsp65/RelA transcription factor

Identifiers

PMID29349898
PMCPMC5894512
OpenAlexW2793423697

What OpenQuestion holds

Textmetadata
LicenceTDM
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.