Evidence map›Paper›PMID 38164587›Full record

ArticleMolecular pharmacology2024

A Constitutive EGFR Kinase Dimer to Study Inhibitor Pharmacology.

Justin J Kim, Ilse K Schaeffner, David E Heppner, Ciric To, Pasi A Jänne, Tyler S Beyett, Michael J Eck

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

Article in Molecular pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 27% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026
    Article
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 1 institution in 1 country.

Justin J KimDepartment of Cancer Biology (J.J.K., I.K.S., T.S.B., M.J.E.), Lowe Center for Thoracic Oncology (C.T., P.A.J.), and Department of Medical Oncology (C.T., P.A.J.), Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Biological Chemistry and Molecular Pharmacology (J.J.K., I.K.S., T.S.B., M.J.E.) and Department of Medicine (C.T., P.A.J.), Harvard Medical School, Boston, Massachusetts; Department of Chemistry, University at Buffalo, Buffalo, New York (D.E.H.); Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York (D.E.H.).ORCID 0009-0000-7393-3758
Ilse K SchaeffnerDepartment of Cancer Biology (J.J.K., I.K.S., T.S.B., M.J.E.), Lowe Center for Thoracic Oncology (C.T., P.A.J.), and Department of Medical Oncology (C.T., P.A.J.), Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Biological Chemistry and Molecular Pharmacology (J.J.K., I.K.S., T.S.B., M.J.E.) and Department of Medicine (C.T., P.A.J.), Harvard Medical School, Boston, Massachusetts; Department of Chemistry, University at Buffalo, Buffalo, New York (D.E.H.); Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York (D.E.H.).
David E HeppnerDepartment of Cancer Biology (J.J.K., I.K.S., T.S.B., M.J.E.), Lowe Center for Thoracic Oncology (C.T., P.A.J.), and Department of Medical Oncology (C.T., P.A.J.), Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Biological Chemistry and Molecular Pharmacology (J.J.K., I.K.S., T.S.B., M.J.E.) and Department of Medicine (C.T., P.A.J.), Harvard Medical School, Boston, Massachusetts; Department of Chemistry, University at Buffalo, Buffalo, New York (D.E.H.); Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York (D.E.H.).
Ciric ToDepartment of Cancer Biology (J.J.K., I.K.S., T.S.B., M.J.E.), Lowe Center for Thoracic Oncology (C.T., P.A.J.), and Department of Medical Oncology (C.T., P.A.J.), Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Biological Chemistry and Molecular Pharmacology (J.J.K., I.K.S., T.S.B., M.J.E.) and Department of Medicine (C.T., P.A.J.), Harvard Medical School, Boston, Massachusetts; Department of Chemistry, University at Buffalo, Buffalo, New York (D.E.H.); Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York (D.E.H.).
Pasi A JänneDepartment of Cancer Biology (J.J.K., I.K.S., T.S.B., M.J.E.), Lowe Center for Thoracic Oncology (C.T., P.A.J.), and Department of Medical Oncology (C.T., P.A.J.), Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Biological Chemistry and Molecular Pharmacology (J.J.K., I.K.S., T.S.B., M.J.E.) and Department of Medicine (C.T., P.A.J.), Harvard Medical School, Boston, Massachusetts; Department of Chemistry, University at Buffalo, Buffalo, New York (D.E.H.); Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York (D.E.H.).
Tyler S BeyettDepartment of Cancer Biology (J.J.K., I.K.S., T.S.B., M.J.E.), Lowe Center for Thoracic Oncology (C.T., P.A.J.), and Department of Medical Oncology (C.T., P.A.J.), Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Biological Chemistry and Molecular Pharmacology (J.J.K., I.K.S., T.S.B., M.J.E.) and Department of Medicine (C.T., P.A.J.), Harvard Medical School, Boston, Massachusetts; Department of Chemistry, University at Buffalo, Buffalo, New York (D.E.H.); Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York (D.E.H.) michael_eck@dfci.harvard.edu tbeyett@emory.edu.ORCID 0000-0001-5509-7004
Michael J EckDepartment of Cancer Biology (J.J.K., I.K.S., T.S.B., M.J.E.), Lowe Center for Thoracic Oncology (C.T., P.A.J.), and Department of Medical Oncology (C.T., P.A.J.), Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Biological Chemistry and Molecular Pharmacology (J.J.K., I.K.S., T.S.B., M.J.E.) and Department of Medicine (C.T., P.A.J.), Harvard Medical School, Boston, Massachusetts; Department of Chemistry, University at Buffalo, Buffalo, New York (D.E.H.); Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York (D.E.H.) michael_eck@dfci.harvard.edu tbeyett@emory.edu.
Roswell Park Comprehensive Cancer Center · US

Funding

University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8M
StructureP01CA154303 · NCI · DANA-FARBER CANCER INST · PI ECK, MICHAEL J · 2012 to 2021
$17.8M
Structure, mechanism, and pharmacology of BRAF and its partners in the RAS/RAF/MAP kinase pathwayR35CA242461 · NCI · DANA-FARBER CANCER INST · PI ECK, MICHAEL J · 2019 to 2025
$7.4M
Development of Combination Therapies to Delay/Prevent Acquired Drug ResistanceR35CA220497 · NCI · DANA-FARBER CANCER INST · PI JANNE, PASI A · 2018 to 2024
$7.2M
Targeting the neuronal microenvironment in glioblastomaU19CA264504 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy T Batchelor · 2021 to 2026
$6.4M
Discovery and optimization of novel mutant-selective allosteric inhibitors of EGFR T790MR01CA201049 · NCI · DANA-FARBER CANCER INST · PI ECK, MICHAEL J, GRAY, NATHANAEL SCHIANDER · 2016 to 2025
$4.6M
Studies of mutant-selective allosteric inhibitors of EGFR for non-small cell lung cancerF32CA247198 · NCI · DANA-FARBER CANCER INST · PI BEYETT, TYLER STEVEN · 2020 to 2022
$196k
NCATS NIH HHS UL1 TR001412NCI NIH HHS F32 CA247198NCI NIH HHS P01 CA154303NCI NIH HHS R01 CA201049NCI NIH HHS R35 CA220497NCI NIH HHS R35 CA242461NCI NIH HHS U19 CA264504
6 · The paper itself

Abstract

Lung cancer is commonly caused by activating mutations in the epidermal growth factor receptor (EGFR). Allosteric kinase inhibitors are unaffected by common ATP-site resistance mutations and represent a promising therapeutic strategy for targeting drug-resistant EGFR variants. However, allosteric inhibitors are antagonized by kinase dimerization, and understanding this phenomenon has been limited to cellular experiments. To facilitate the study of allosteric inhibitor pharmacology, we designed and purified a constitutive EGFR kinase dimer harboring the clinically relevant L858R/T790M mutations. Kinetic characterization revealed that the EGFR kinase dimer is more active than monomeric EGFR(L858R/T790M) kinase and has the same K

Indexed as

ErbB ReceptorsLung NeoplasmsAdenosine TriphosphateDrug Resistance, NeoplasmHumansMutationProtein Kinase InhibitorsAdenosine TriphosphateEGFR protein, humanErbB ReceptorsProtein Kinase Inhibitors

Identifiers

PMID38164587
PMCPMC10794983
OpenAlexW4389475254

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.