Evidence map›Paper›PMID 39177932›Full record

ArticleBreast cancer research and treatment2024

Phosphoenolpyruvate carboxykinase-2 (PCK2) is a therapeutic target in triple-negative breast cancer.

Vignesh Gunasekharan, Hao-Kuen Lin, Michal Marczyk, Alejandro Rios-Hoyo, Gerson Espinoza Campos, Naing Lin Shan, Mostafa Ahmed, Sheila Umlauf, Peter Gareiss, Raaisa Raaisa and 6 more

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Article in Breast cancer research and treatment, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Cancer biology & therapy · 2025
    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

16 authors.

Vignesh GunasekharanYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Hao-Kuen LinYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Michal MarczykYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Alejandro Rios-HoyoYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Gerson Espinoza CamposYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Naing Lin ShanYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Mostafa AhmedAtomwise, San Francisco, CA, USA.
Sheila UmlaufYale Center for Molecular Discovery, Yale University, West Haven, CT, USA.
Peter GareissYale Center for Molecular Discovery, Yale University, West Haven, CT, USA.
Raaisa RaaisaYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Richard WilliamsYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Rebecca CardoneYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Stephan SiebelYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Richard KibbeyYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA.
Yulia V SurovtsevaYale Center for Molecular Discovery, Yale University, West Haven, CT, USA.
Lajos PusztaiYale Cancer Center, Yale School of Medicine, 300 George Street, Suite 120, Rm 133, New Haven, CT, 06511, USA. lajos.pusztai@yale.edu.

Funding

Breast Cancer Research Foundation investigator award BCRF-22-133Susan Komen Leadership Grant SAC220225
6 · The paper itself

Abstract

purposeMetabolic rewiring in malignant transformation is often accompanied by altered expression of metabolic isozymes. Phosphoenolpyruvate carboxykinase-2 (PCK2) catalyzes the rate-limiting step of gluconeogenesis and is the dominant isoform in many cancers including triple-negative breast cancer (TNBC). Our goal was to identify small molecule inhibitors of PCK2 enzyme activity.

methodsWe assessed the impact of PCK2 down regulation with shRNA on TNBC cell growth in vitro and used AtomNet® deep convolutional neural network software to identify potential small molecule inhibitors of PCK2-based structure. We iteratively tested candidate compounds in an in vitro PCK-2 enzyme assay. The impact of the top hit on metabolic flux and cell viability was also assessed.

resultsPCK2 downregulation decreased growth of BT-549 and MDA-MB-231 cells and reduced metabolic flux through pyruvate carboxylase. The first AtomNet® in silico structural screen of 7 million compounds yielded 86 structures that were tested in PCK2 enzyme assay in vitro. The top hit (IC

conclusion3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate is a high affinity PCK2 enzyme inhibitor that also has significant growth inhibitory activity in breast cell lines in vitro and represents a potential therapeutic lead compound.

Indexed as

Cell ProliferationPhosphoenolpyruvate Carboxykinase (GTP)Triple Negative Breast NeoplasmsAntineoplastic AgentsCell Line, TumorCell SurvivalEnzyme InhibitorsFemaleHumansPhosphoenolpyruvate Carboxykinase (ATP)Small Molecule LibrariesAntineoplastic AgentsEnzyme InhibitorsPCK2 protein, humanPhosphoenolpyruvate Carboxykinase (ATP)Phosphoenolpyruvate Carboxykinase (GTP)Small Molecule LibrariesArtificial intelligenceDrug screenLoss of Isozyme DiversityPCK2TNBC therapy

Identifiers

PMID39177932

What OpenQuestion holds

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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.