Evidence map›Paper›PMID 30122040›Full record

ArticleJournal of medicinal chemistry2018

Replacement of a Naphthalene Scaffold in Kelch-like ECH-Associated Protein 1 (KEAP1)/Nuclear Factor (Erythroid-derived 2)-like 2 (NRF2) Inhibitors.

Benjamin G Richardson, Atul D Jain, Haranatha R Potteti, Phillip R Lazzara, Brian P David, Chandra R Tamatam, Ewelina Choma, Kornelia Skowron, Katherine Dye, Zamia Siddiqui and 4 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 49 citations in OpenAlex.

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  13. A multicomponent tetrazolo indole synthesis.Chemical communications (Cambridge, England) · 2021
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  19. Nrf2 activation through the inhibition of Keap1-Nrf2 protein-protein interaction.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2020
    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

14 authors at 1 institution in 1 country.

Benjamin G RichardsonDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy , ‡Department of Pediatrics, College of Medicine , §UICentre for Drug Discovery , ⊥Mass Spectrometry Core at Research Resources Center , #University of Illinois Cancer Center , University of Illinois at Chicago , 833 South Wood Street , Chicago , Illinois 60612 , United States.ORCID 0000-0001-6003-3021
Atul D JainDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy , ‡Department of Pediatrics, College of Medicine , §UICentre for Drug Discovery , ⊥Mass Spectrometry Core at Research Resources Center , #University of Illinois Cancer Center , University of Illinois at Chicago , 833 South Wood Street , Chicago , Illinois 60612 , United States.
Haranatha R Potteti
Phillip R LazzaraDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy , ‡Department of Pediatrics, College of Medicine , §UICentre for Drug Discovery , ⊥Mass Spectrometry Core at Research Resources Center , #University of Illinois Cancer Center , University of Illinois at Chicago , 833 South Wood Street , Chicago , Illinois 60612 , United States.
Brian P DavidDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy , ‡Department of Pediatrics, College of Medicine , §UICentre for Drug Discovery , ⊥Mass Spectrometry Core at Research Resources Center , #University of Illinois Cancer Center , University of Illinois at Chicago , 833 South Wood Street , Chicago , Illinois 60612 , United States.ORCID 0000-0001-5328-5394
Chandra R Tamatam
Ewelina ChomaDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy , ‡Department of Pediatrics, College of Medicine , §UICentre for Drug Discovery , ⊥Mass Spectrometry Core at Research Resources Center , #University of Illinois Cancer Center , University of Illinois at Chicago , 833 South Wood Street , Chicago , Illinois 60612 , United States.
Kornelia SkowronDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy , ‡Department of Pediatrics, College of Medicine , §UICentre for Drug Discovery , ⊥Mass Spectrometry Core at Research Resources Center , #University of Illinois Cancer Center , University of Illinois at Chicago , 833 South Wood Street , Chicago , Illinois 60612 , United States.
Katherine Dye
Zamia SiddiquiDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy , ‡Department of Pediatrics, College of Medicine , §UICentre for Drug Discovery , ⊥Mass Spectrometry Core at Research Resources Center , #University of Illinois Cancer Center , University of Illinois at Chicago , 833 South Wood Street , Chicago , Illinois 60612 , United States.
Yue-Ting Wang
Aleksej KrunicDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy , ‡Department of Pediatrics, College of Medicine , §UICentre for Drug Discovery , ⊥Mass Spectrometry Core at Research Resources Center , #University of Illinois Cancer Center , University of Illinois at Chicago , 833 South Wood Street , Chicago , Illinois 60612 , United States.
Sekhar P Reddy
Terry W MooreDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy , ‡Department of Pediatrics, College of Medicine , §UICentre for Drug Discovery , ⊥Mass Spectrometry Core at Research Resources Center , #University of Illinois Cancer Center , University of Illinois at Chicago , 833 South Wood Street , Chicago , Illinois 60612 , United States.ORCID 0000-0002-5410-306X
University of Illinois Chicago · US

Funding

Role of Nrf2 in Alveolar Epithelial Cell Regeneration During Lung RepairR01HL136946 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI REDDY, SEKHAR P. · 2017 to 2020
$2.1M
Non-Covalent Nrf2 Activators for the Treatment of Chronic WoundsR01AR069541 · NIAMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MOORE, TERRY WILLIAM · 2017 to 2019
$1.0M
NHLBI NIH HHS R01 HL136946NIAMS NIH HHS R01 AR069541
6 · The paper itself

Abstract

Activators of nuclear factor-erythroid 2-related factor 2 (NRF2) could lead to promising therapeutics for prevention and treatment of oxidative stress and inflammatory disorders. Ubiquitination and subsequent degradation of the transcription factor NRF2 is mediated by Kelch-like ECH-associated protein-1 (KEAP1). Inhibition of the KEAP1/NRF2 interaction with small molecules leads to NRF2 activation. Previously, we and others described naphthalene-based NRF2 activators, but the 1,4-diaminonaphthalene scaffold may not represent a drug-like scaffold. Paying particular attention to aqueous solubility, metabolic stability, potency, and mutagenicity, we modified a previously known, naphthalene-based nonelectrophilic NRF2 activator to give a series of non-naphthalene and heterocyclic scaffolds. We found that, compared to previously reported naphthalene-based compounds, a 1,4-isoquinoline scaffold provides a better mutagenic profile without sacrificing potency, stability, or solubility.

Indexed as

Cells, CulturedGene Expression RegulationHumansIsoquinolinesKelch-Like ECH-Associated Protein 1KeratinocytesMutagenesisNaphthalenesNF-E2-Related Factor 2Protein Interaction Domains and MotifsSalmonella typhimuriumSmall Molecule LibrariesIsoquinolinesKEAP1 protein, humanKelch-Like ECH-Associated Protein 1naphthaleneNaphthalenesNFE2L2 protein, humanNF-E2-Related Factor 2Small Molecule Libraries

Identifiers

PMID30122040
PMCPMC6190829
OpenAlexW2888177847

What OpenQuestion holds

Textmetadata
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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.