Evidence map›Paper›PMID 30643281›Full record

ArticleNature chemical biology2019

Discovery of a ZIP7 inhibitor from a Notch pathway screen.

Erin Nolin, Sara Gans, Luis Llamas, Somnath Bandyopadhyay, Scott M Brittain, Paula Bernasconi-Elias, Kyle P Carter, Joseph J Loureiro, Jason R Thomas, Markus Schirle and 33 more

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

45 citing papers in PubMed, 66 citations in OpenAlex.

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  11. Decoding the Implications of Zinc in the Development and Therapy of Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  12. Metal Ion Signaling in Biomedicine.Chemical reviews · 2025
    Review
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  17. The ZnDevelopmental cell · 2024
    Article
  18. Review
  19. CAD204520 TargetsInternational journal of molecular sciences · 2024
    Article
  20. Review
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

43 authors at 4 institutions in 3 countries.

Erin NolinNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Sara GansNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Luis LlamasNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Somnath BandyopadhyayNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Scott M BrittainNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Paula Bernasconi-EliasNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Kyle P CarterDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado, Boulder, CO, USA.
Joseph J LoureiroNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Jason R ThomasNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Markus SchirleNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Yi YangNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Ning GuoNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Guglielmo RomaNovartis Institutes for Biomedical Research, Basel, Switzerland.ORCID http://orcid.org/0000-0002-8020-4219
Sven SchuiererNovartis Institutes for Biomedical Research, Basel, Switzerland.
Martin BeibelNovartis Institutes for Biomedical Research, Basel, Switzerland.
Alicia LindemanNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Frederic SigoillotNovartis Institutes for Biomedical Research, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8695-4838
Amy ChenNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Kevin X XieNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Samuel HoNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
John Reece-HoyesNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Wilhelm A WeihofenNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Kayla TyskiewiczNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Dominic HoepfnerNovartis Institutes for Biomedical Research, Basel, Switzerland.ORCID http://orcid.org/0000-0001-8450-7543
Richard I McDonaldNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Nicolette GuthrieNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Abhishek DograNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Haibing GuoNovartis Institutes for Biomedical Research, Shanghai, China.
Jian ShaoNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Jian DingNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Stephen M CanhamNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Geoff BoyntonNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Elizabeth L GeorgeNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Zhao B KangNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Christophe AntczakNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Jeffery A PorterNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Owen WallaceNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
John A TallaricoNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Amy E PalmerDepartment of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado, Boulder, CO, USA.ORCID http://orcid.org/0000-0002-5794-5983
Jeremy L JenkinsNovartis Institutes for Biomedical Research, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9795-0771
Rishi K JainNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Simon M BushellNovartis Institutes for Biomedical Research, Cambridge, MA, USA. simon.bushell@novartis.com.ORCID http://orcid.org/0000-0002-8945-2972
Christy J FryerNovartis Institutes for Biomedical Research, Cambridge, MA, USA. christy.fryer@novartis.com.ORCID http://orcid.org/0000-0002-5772-6393
Novartis (United States) · USNovartis (Switzerland) · CHNovartis (China) · CNUniversity of Colorado Boulder · US

Funding

Regulation of Cell Signaling by Transition Metal DynamicsDP1GM114863 · NIGMS · UNIVERSITY OF COLORADO · PI PALMER, AMY E · 2014 to 2018
$3.8M
NIGMS NIH HHS DP1 GM114863
6 · The paper itself

Abstract

The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway. A phenotypic screen identified compounds that interfere with trafficking of Notch and induce apoptosis via an endoplasmic reticulum (ER) stress mechanism. Target identification approaches revealed a role for SLC39A7 (ZIP7), a zinc transport family member, in governing Notch trafficking and signaling. Generation and sequencing of a compound-resistant cell line identified a V430E mutation in ZIP7 that confers transferable resistance to the compound NVS-ZP7-4. NVS-ZP7-4 altered zinc in the ER, and an analog of the compound photoaffinity labeled ZIP7 in cells, suggesting a direct interaction between the compound and ZIP7. NVS-ZP7-4 is the first reported chemical tool to probe the impact of modulating ER zinc levels and investigate ZIP7 as a novel druggable node in the Notch pathway.

Indexed as

AnimalsApoptosisCarrier ProteinsCation Transport ProteinsCell LineCell Transformation, NeoplasticEndoplasmic ReticulumEndoplasmic Reticulum StressHumansMutationProtein TransportReceptor, Notch1Signal TransductionZincCarrier ProteinsCation Transport ProteinsReceptor, Notch1SLC39A7 protein, humanZinczinc-binding protein

Identifiers

PMID30643281
PMCPMC7251565
OpenAlexW2908216418

What OpenQuestion holds

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Registered trials

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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.