Evidence map›Paper›PMID 31745079›Full record

ArticleNature communications2019

Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo.

Tamer S Kaoud, William H Johnson, Nancy D Ebelt, Andrea Piserchio, Diana Zamora-Olivares, Sabrina X Van Ravenstein, Jacey R Pridgen, Ramakrishna Edupuganti, Rachel Sammons, Micael Cano and 10 more

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

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-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

14 citing papers in PubMed, 30 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

20 authors at 7 institutions in 3 countries.

Tamer S KaoudDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.ORCID http://orcid.org/0000-0003-1298-8725
William H JohnsonDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.
Nancy D EbeltDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.ORCID http://orcid.org/0000-0002-1998-3719
Andrea PiserchioDepartment of Chemistry and Biochemistry, The City College of New York, New York, NY, USA.ORCID http://orcid.org/0000-0001-7865-9065
Diana Zamora-OlivaresDepartment of Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.
Sabrina X Van RavensteinDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.ORCID http://orcid.org/0000-0002-5396-5100
Jacey R PridgenDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.ORCID http://orcid.org/0000-0002-4117-7166
Ramakrishna EdupugantiDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.
Rachel SammonsDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.ORCID http://orcid.org/0000-0003-4211-0083
Micael CanoDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.
Mangalika WarthakaDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.
Matthew HargerBiomedical Engineering Department, The University of Texas at Austin, Austin, TX, USA.
Clint D J TavaresDepartment of Cancer Biology, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA.
Jihyun ParkThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mohamed F RadwanDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.ORCID http://orcid.org/0000-0003-2714-0962
Pengyu RenBiomedical Engineering Department, The University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0002-5613-1910
Eric V AnslynDepartment of Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.ORCID http://orcid.org/0000-0002-5137-8797
Kenneth Y TsaiMoffitt Cancer Center, Tampa, FL, USA.ORCID http://orcid.org/0000-0001-5325-212X
Ranajeet GhoseDepartment of Chemistry and Biochemistry, The City College of New York, New York, NY, USA.
Kevin N DalbyDivision of Chemical Biology and Medicinal Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA. dalby@austin.utexas.edu.ORCID http://orcid.org/0000-0001-9272-5129
The University of Texas at Austin · USCity College of New York · USHarvard University · USKing Abdulaziz University · SAMoffitt Cancer Center · USThe Graduate Center, CUNY · USThe University of Texas MD Anderson Cancer Center · US

Funding

Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
Regulation of eEF-2K an Energy and Nutrient SensorR01GM123252 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI DALBY, KEVIN N, GHOSE, RANAJEET · 2017 to 2024
$2.7M
NIGMS NIH HHS P41 GM103311NIGMS NIH HHS R01 GM123252
6 · The paper itself

Abstract

Recently, the targeting of ERK with ATP-competitive inhibitors has emerged as a potential clinical strategy to overcome acquired resistance to BRAF and MEK inhibitor combination therapies. In this study, we investigate an alternative strategy of targeting the D-recruitment site (DRS) of ERK. The DRS is a conserved region that lies distal to the active site and mediates ERK-protein interactions. We demonstrate that the small molecule BI-78D3 binds to the DRS of ERK2 and forms a covalent adduct with a conserved cysteine residue (C159) within the pocket and disrupts signaling in vivo. BI-78D3 does not covalently modify p38MAPK, JNK or ERK5. BI-78D3 promotes apoptosis in BRAF inhibitor-naive and resistant melanoma cells containing a BRAF V600E mutation. These studies provide the basis for designing modulators of protein-protein interactions involving ERK, with the potential to impact ERK signaling dynamics and to induce cell cycle arrest and apoptosis in ERK-dependent cancers.

Indexed as

Xenograft Model Antitumor AssaysAnimalsApoptosisBinding SitesCell Line, TumorCysteineDioxanesHEK293 CellsHumansMAP Kinase Signaling SystemMelanomaMice, NudeMitogen-Activated Protein Kinase 1Molecular Dynamics SimulationProtein BindingProtein Kinase Inhibitors4-(2,3-dihydro-1,4-benzodioxin-6-yl)-2,4-dihydro-5-((5-nitro-2-thiazolyl)thio)-3H-1,2,4-triazol-3-oneCysteineDioxanesMAPK1 protein, humanMitogen-Activated Protein Kinase 1Protein Kinase InhibitorsThiazoles

Identifiers

PMID31745079
PMCPMC6863825
OpenAlexW2990996987

What OpenQuestion holds

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LicenceCC BY
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.