Evidence map›Paper›PMID 39675702›Full record

ArticleThe Journal of biological chemistry2025

An SH3-binding allosteric modulator stabilizes the global conformation of the AML-associated Src-family kinase, Hck.

Ari M Selzer, Gabriella Gerlach, Giancarlo Gonzalez-Areizaga, Thomas E Wales, Stephanie Y Cui, Prema Iyer, John R Engen, Carlos Camacho, Rieko Ishima, Thomas E Smithgall

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

10 authors.

Ari M SelzerDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Gabriella GerlachDepartment of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Giancarlo Gonzalez-AreizagaDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Thomas E WalesDepartment of Chemistry and Chemical Biology, College of Science, Northeastern University, Boston, Massachusetts, USA.
Stephanie Y CuiDepartment of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.
Prema IyerDepartment of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.
John R EngenDepartment of Chemistry and Chemical Biology, College of Science, Northeastern University, Boston, Massachusetts, USA.
Carlos CamachoDepartment of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Rieko IshimaDepartment of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Thomas E SmithgallDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. Electronic address: tsmithga@pitt.edu.

Funding

Precision Targeting of Myeloid Src-family Kinases in Acute Myelogenous LeukemiaR01CA233576 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SMITHGALL, THOMAS E. · 2019 to 2023
$2.4M
Allosteric Modulators of Src-family Kinases for Acute Myeloid LeukemiaF31CA265294 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SELZER, ARI · 2021 to 2023
$92k
NCI NIH HHS F31 CA265294NCI NIH HHS R01 CA233576
6 · The paper itself

Abstract

While ATP-site inhibitors for protein-tyrosine kinases are often effective drugs, their clinical utility can be limited by off-target activity and acquired resistance mutations due to the conserved nature of the ATP-binding site. However, combining ATP-site and allosteric kinase inhibitors can overcome these shortcomings in a double-drugging framework. Here we explored the allosteric effects of two pyrimidine diamines, PDA1 and PDA2, on the conformational dynamics and activity of the Src-family tyrosine kinase Hck, a promising drug target for acute myeloid leukemia. Using

Indexed as

Leukemia, Myeloid, AcuteProtein Kinase InhibitorsProto-Oncogene Proteins c-hckPyrimidinessrc Homology DomainsAllosteric RegulationBinding SitesHumansMolecular Dynamics SimulationProtein ConformationHCK protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins c-hckPyrimidineshydrogen-deuterium exchange mass spectrometrykinase inhibitorsNMRSH2 domainSH3 domainSrc-family kinasetyrosine kinases

Identifiers

PMID39675702
PMCPMC11786751

What OpenQuestion holds

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LicenceCC BY
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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.