Evidence map›Paper›PMID 37588763›Full record

ArticleACS pharmacology & translational science2023

First-in-Class NADH/Ubiquinone Oxidoreductase Core Subunit S7 (NDUFS7) Antagonist for the Treatment of Pancreatic Cancer.

Yibin Xu, Ding Xue, Armita Kyani, Armand Bankhead, Joyeeta Roy, Mats Ljungman, Nouri Neamati

Abstract read
In one paragraph

Article in ACS pharmacology & translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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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

7 authors.

Yibin XuDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.ORCID https://orcid.org/0000-0002-8261-3286
Ding XueDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.ORCID https://orcid.org/0000-0002-7870-0408
Armita KyaniDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
Armand BankheadRogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States.
Joyeeta RoyDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.ORCID https://orcid.org/0000-0002-4904-0551
Mats LjungmanRogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States.
Nouri NeamatiDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.ORCID https://orcid.org/0000-0003-3291-7131

Funding

ROS-targeted therapy for pancreatic cancer - Diversity SupplementR01CA188252 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NEAMATI, NOURI · 2015 to 2020
$2.6M
Preclinical Development of First-in-Class NDUFS7 Antagonists for the Treatment of Pancreatic CancerR01CA272641 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NOURI NEAMATI · 2022 to 2026
$2.3M
NCI NIH HHS R01 CA188252NCI NIH HHS R01 CA272641
6 · The paper itself

Abstract

Pancreatic cancer cells adapt to nutrient-scarce metabolic conditions by increasing their oxidative phosphorylation reserve to survive. Here, we present a first-in-class small-molecule NDUFS7 antagonist that inhibits oxidative phosphorylation (OXPHOS) for the treatment of pancreatic cancer. The lead compound, DX2-201, suppresses the proliferation of a panel of cell lines, and a metabolically stable analogue, DX3-213B, shows significant efficacy in a syngeneic model of pancreatic cancer. Exome sequencing of six out of six clones resistant to DX2-201 revealed a pV91M mutation in NDUFS7, providing direct evidence of its drug-binding site. In combination studies, DX2-201 showed synergy with multiple metabolic modulators, select OXPHOS inhibitors, and PARP inhibitors. Importantly, a combination with 2-deoxyglucose overcomes drug resistance in vivo. This study demonstrates that an efficacious treatment for pancreatic cancer can be achieved through inhibition of OXPHOS and direct binding to NDUFS7, providing a novel therapeutic strategy for this hard-to-treat cancer.

Identifiers

PMID37588763
PMCPMC10425995

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.