Evidence map›Paper›PMID 25757568›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage.

Oscar Sasso, Marco Migliore, Damien Habrant, Andrea Armirotti, Clara Albani, Maria Summa, Guillermo Moreno-Sanz, Rita Scarpelli, Daniele Piomelli

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
9.6field-weighted citation impact, top 2% 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

34 citing papers in PubMed, 61 citations in OpenAlex.

  1. Sulfide regulation and catabolism in health and disease.Signal transduction and targeted therapy · 2025
    Review
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  5. Design, synthesis andJournal of enzyme inhibition and medicinal chemistry · 2021
    Article
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  8. Comorbid anxiety-like behavior in a rat model of colitis is mediated by an upregulation of corticolimbic fatty acid amide hydrolase.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021
    Article
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  10. Article
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  13. Review
  14. Novel Analgesics with Peripheral Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020
    Review
  15. Article
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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

9 authors at 3 institutions in 2 countries.

Oscar Sasso*Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; and Departments of Anatomy and Neurobiology and Pharmacology and Biological Chemistry, University of California-Irvine, Irvine, California, USA.
Marco Migliore*Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; and Departments of Anatomy and Neurobiology and Pharmacology and Biological Chemistry, University of California-Irvine, Irvine, California, USA.
Damien Habrant*Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; and Departments of Anatomy and Neurobiology and Pharmacology and Biological Chemistry, University of California-Irvine, Irvine, California, USA.
Andrea Armirotti*Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; and Departments of Anatomy and Neurobiology and Pharmacology and Biological Chemistry, University of California-Irvine, Irvine, California, USA.
Clara Albani*Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; and Departments of Anatomy and Neurobiology and Pharmacology and Biological Chemistry, University of California-Irvine, Irvine, California, USA.
Maria Summa*Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; and Departments of Anatomy and Neurobiology and Pharmacology and Biological Chemistry, University of California-Irvine, Irvine, California, USA.
Guillermo Moreno-Sanz*Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; and Departments of Anatomy and Neurobiology and Pharmacology and Biological Chemistry, University of California-Irvine, Irvine, California, USA.
Rita Scarpelli*Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; and Departments of Anatomy and Neurobiology and Pharmacology and Biological Chemistry, University of California-Irvine, Irvine, California, USA.
Daniele Piomelli*Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy; and Departments of Anatomy and Neurobiology and Pharmacology and Biological Chemistry, University of California-Irvine, Irvine, California, USA piomelli@uci.edu.
Italian Institute of Technology · ITIrvine University · USUniversity of California, Irvine · US

Funding

Characterization of Anandamide Transport in BrainR01DA012413 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI PIOMELLI, DANIELE · 1998 to 2016
$4.7M
NIDA NIH HHS DA012413NIDA NIH HHS R01 DA012413
6 · The paper itself

Abstract

The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these drugs, as well as their propensity to damage the gastrointestinal (GI) epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and promotes GI healing. Here, we describe the first class of systemically active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity. The class prototype 4: (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 ± 0.002 µM; Cox-1, 0.012 ± 0.002 µM; and Cox-2, 0.43 ± 0.025 µM) but does not significantly interact with a panel of >100 off targets. After oral administration in mice, ARN2508 engages its intended targets and exerts profound therapeutic effects in models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric damage and indeed protects the GI from NSAID-induced damage through a mechanism that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive.

Indexed as

AmidohydrolasesAnimalsAnti-Inflammatory Agents, Non-SteroidalCarrageenanCyclooxygenase 1Cyclooxygenase 2Enzyme InhibitorsFatty Acid Amide HydrolasesGastrointestinal DiseasesGastrointestinal TractInflammationIntestinesMiceMolecular StructurePhenylcarbamatesPhenylpropionatesAmidohydrolasesAnti-Inflammatory Agents, Non-SteroidalARN2508CarrageenanCyclooxygenase 1Cyclooxygenase 2Enzyme InhibitorsFatty Acid Amide HydrolasesPhenylcarbamatesPhenylpropionatesanandamidecannabinoid receptorinflammatory bowel diseasemultitarget inhibitors

Identifiers

PMID25757568
PMCPMC4447230
OpenAlexW2019144812

What OpenQuestion holds

Textmetadata
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.