Evidence map›Paper›PMID 30832411›Full record

ArticleCancers2019

The Novel Mnk1/2 Degrader and Apoptosis Inducer VNLG-152 Potently Inhibits TNBC Tumor Growth and Metastasis.

Senthilmurugan Ramalingam, Vidya P Ramamurthy, Lalji K Gediya, Francis N Murigi, Puranik Purushottamachar, Weiliang Huang, Eun Yong Choi, Yuji Zhang, Tadas S Vasaitis, Maureen A Kane and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.1field-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

17 citing papers in PubMed, 27 citations in OpenAlex.

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  14. The MNK1/2-eIF4E Axis as a Potential Therapeutic Target in Melanoma.International journal of molecular sciences · 2020
    Review
  15. Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer.International journal of molecular sciences · 2020
    Review
  16. Article
  17. 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

12 authors at 2 institutions in 1 country.

Senthilmurugan RamalingamDepartment of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA. SRamalingam@som.umaryland.edu.
Vidya P RamamurthyDepartment of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA. rv.darsini@gmail.com.ORCID 0000-0001-6902-0921
Lalji K GediyaDepartment of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA. lalji.gediya@gmail.com.
Francis N MurigiDepartment of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA. njamurigi@gmail.com.
Puranik PurushottamacharDepartment of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA. PPuranik@som.umaryland.edu.
Weiliang HuangDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201-1559, USA. whuang@rx.umaryland.edu.
Eun Yong ChoiMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA. echoi@som.umaryland.edu.
Yuji ZhangDivision of Biostatistics and Bioinformatics, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201-1559, USA. Yuzhang@som.umaryland.edu.
Tadas S VasaitisDepartment of Pharmaceutical Sciences, School of Pharmacy and Health Professions, University of Maryland Eastern Shore, 207 Somerset Hall, Princess Anne, MD 21853, USA. tsvasaitis@umes.edu.
Maureen A KaneDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201-1559, USA. mkane@rx.umaryland.edu.
Rena G LapidusMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA. rlapidus@som.umaryland.edu.
Vincent C O NjarDepartment of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA. vnjar@som.umaryland.edu.
University of Maryland, Baltimore · USUniversity of Maryland Eastern Shore · US

Funding

Development of Next Generation Galeterone Analogs for Prostate Cancer TherapyR01CA224696 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI NJAR, VINCENT COLLINS OFUKA · 2018 to 2022
$2.6M
NCI NIH HHS R01 CA224696NIH HHS R01CA129379, R21195694, and R01CA224696
6 · The paper itself

Abstract

Currently, there are no effective therapies for patients with triple-negative breast cancer (TNBC), an aggressive and highly metastatic disease. Activation of eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (Mnk1/2) play a critical role in the development, progression and metastasis of TNBC. Herein, we undertook a comprehensive study to evaluate the activity of a first-in-class Mnk1/2 protein degraders, racemic VNLG-152R and its two enantiomers (VNLG-152E1 and VNLG-152E2) in in vitro and in vivo models of TNBC. These studies enabled us to identify racemic VNLG-152R as the most efficacious Mnk1/2 degrader, superior to its pure enantiomers. By targeting Mnk1/2 protein degradation (activity), VNLG-152R potently inhibited both Mnk-eIF4E and mTORC1 signaling pathways and strongly regulated downstream factors involved in cell cycle regulation, apoptosis, pro-inflammatory cytokines/chemokines secretion, epithelial-mesenchymal transition (EMT) and metastasis. Most importantly, orally bioavailable VNLG-152R exhibited remarkable antitumor (91 to 100% growth inhibition) and antimetastatic (~80% inhibition) activities against cell line and patient-derived TNBC xenograft models, with no apparent host toxicity. Collectively, these studies demonstrate that targeting Mnk-eIF4E/mTORC1 signaling with a potent Mnk1/2 degrader, VNLG-152R, is a novel therapeutic strategy that can be developed as monotherapy for the effective treatment of patients with primary/metastatic TNBC.

Indexed as

apoptosismetastasisMnk1/2 degradersMnk-eIF4E/mTORC1 signaling pathwaystriple negative breast cancerVNLG-152R

Identifiers

PMID30832411
PMCPMC6468747
OpenAlexW2918790645

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.