Evidence map›Paper›PMID 31734178›Full record

ArticleCell chemical biology2020

Metabolic Modifier Screen Reveals Secondary Targets of Protein Kinase Inhibitors within Nucleotide Metabolism.

Evan R Abt, Ethan W Rosser, Matthew A Durst, Vincent Lok, Soumya Poddar, Thuc M Le, Arthur Cho, Woosuk Kim, Liu Wei, Janet Song and 10 more

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

Article in Cell chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Myricetin InhibitsCells · 2026
    Article
  3. Article
  4. Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Adipose tissue releases nucleosides.American journal of physiology. Cell physiology · 2026
    Article
  6. DNA Content and DNA Damage in Raw and Heat-Processed Foods.Journal of agricultural and food chemistry · 2025
    Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Transcriptome Analysis Reveals the Role of Sucrose in the Production ofInternational journal of molecular sciences · 2024
    Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. 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

20 authors at 4 institutions in 2 countries.

Evan R AbtDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Ethan W RosserAhmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA; Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.
Matthew A DurstDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA; The Jesse Brown VA Medical Center, Chicago, IL, USA.
Vincent LokDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Soumya PoddarDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Thuc M LeDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Arthur ChoDepartment of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Woosuk KimDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Liu WeiDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Janet SongDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Joseph R CapriDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Shili XuAhmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA.
Nanping WuAhmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA.
Roger SlavikDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Michael E JungDepartment of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.
Robert DamoiseauxDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; California NanoSystems Institute, University of California Los Angeles, Los Angeles, CA, USA.
Johannes CzerninDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA.
Timothy R DonahueDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.
Arnon LavieDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA; The Jesse Brown VA Medical Center, Chicago, IL, USA.
Caius G RaduDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: cradu@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Illinois Chicago · USCalifornia NanoSystems Institute · USYonsei University · KR

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
Targeting KRAS and adenosine mediated immunosuppression in pancreatic cancerR01CA260678 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DONAHUE, TIMOTHY R, RADU, CAIUS GABRIEL · 2021 to 2025
$3.0M
PET Imaging-guided Personalized Therapy in Pancreatic CancerR01CA187678 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CZERNIN, JOHANNES, DONAHUE, TIMOTHY R · 2014 to 2018
$2.8M
Expanding the efficacy of asparaginase to solid tumorsI01BX001919 · VA · JESSE BROWN VA MEDICAL CENTER · PI LAVIE, ARNON · 2013 to 2025
–
BLRD VA I01 BX001919NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA187678NCI NIH HHS R01 CA260678NCI NIH HHS T32 CA009120
6 · The paper itself

Abstract

Biosynthesis of the pyrimidine nucleotide uridine monophosphate (UMP) is essential for cell proliferation and is achieved by the activity of convergent de novo and salvage metabolic pathways. Here we report the development and application of a cell-based metabolic modifier screening platform that leverages the redundancy in pyrimidine metabolism for the discovery of selective UMP biosynthesis modulators. In evaluating a library of protein kinase inhibitors, we identified multiple compounds that possess nucleotide metabolism modifying activity. The JNK inhibitor JNK-IN-8 was found to potently inhibit nucleoside transport and engage ENT1. The PDK1 inhibitor OSU-03012 (also known as AR-12) and the RAF inhibitor TAK-632 were shown to inhibit the therapeutically relevant de novo pathway enzyme DHODH and their affinities were unambiguously confirmed through in vitro assays and co-crystallization with human DHODH.

Indexed as

Binding SitesCell Line, TumorCell SurvivalCrystallography, X-RayDihydroorotate DehydrogenaseDrug DesignEquilibrative Nucleoside Transporter 1HumansMolecular Dynamics SimulationOxidoreductases Acting on CH-CH Group DonorsProtein Kinase InhibitorsPyrimidine NucleosidesSmall Molecule LibrariesDihydroorotate DehydrogenaseEquilibrative Nucleoside Transporter 1Oxidoreductases Acting on CH-CH Group DonorsProtein Kinase InhibitorsPyrimidine NucleosidesSmall Molecule Librariescancer metabolismphenotypic screeningpyrimidine metabolismtarget identification

Identifiers

PMID31734178
PMCPMC7035983
OpenAlexW2986758738

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.