ArticleNature chemical biology2020
Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice.
Open access · bronzeAbstract read
In one paragraph
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
8.4field-weighted citation impact, top 2% of its field
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.
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.
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Genetics of methamphetamine use disorder: A systematic review and meta-analyses of gene association studies.Neuroscience and biobehavioral reviews · 2021Pooled it
- Sterol carrier protein 2 loss reduces anxiety and enhances fear extinction.Journal of affective disorders · 2026Article
- Hepatic stearoyl-CoA desaturase 1 suppresses diet-induced hyperphagia and hepatic lipid accumulation through PPARα activation and ketone body signaling.The Journal of biological chemistry · 2026Article
- N-Arachidonoyl-phosphatidylethanolamide phospholipase D activation by muscarinic receptors.The Journal of physiology · 2026Article
- NAPE-PLD: the healthy intersection of N-acylethanolamines and bile acids in physiology and diseases.Pflugers Archiv : European journal of physiology · 2026Review
- The Pharmacological Profile of Plant-Derived Cannabinoids In Vitro.Current topics in behavioral neurosciences · 2026Review
- Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026Review
- Genetic deletion of NAPE-PLD alters stress responsiveness and HPA-axis functionality in a context-dependent manner in mice.Neuropharmacology · 2025Article
- Mice lacking the endocannabinoid-synthesizing enzyme NAPE-PLD exhibit sex-dependent dysregulations in responsiveness to oxycodone and a natural reward.Neuropharmacology · 2025Article
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Photoaffinity Labeling Reveals a Role for the Unusual Triply Acylated PhospholipidJournal of the American Chemical Society · 2025Article
- De Novo Transcriptome Assembly and Annotation Elucidate the Response to Extreme Temperature Stress in the Intermediate HostInternational journal of molecular sciences · 2025Article
- 20:4-NAPE induced changes of mechanical sensitivity and DRG neurons excitability are concentration dependent and mediated via NAPE-PLD.Scientific reports · 2025Article
- Real-time fear emotion recognition in mice based on multimodal data fusion.Scientific reports · 2025Article
- Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice.Cell · 2025Article
- A human gutScience (New York, N.Y.) · 2024Article
- A Highly Potent, Orally Bioavailable Pyrazole-Derived Cannabinoid CB2 Receptor- Selective Full Agonist forACS pharmacology & translational science · 2024Article
- Presynaptic nanoscale components of retrograde synaptic signaling.Science advances · 2024Article
- NAPE-PLD in the ventral tegmental area regulates reward events, feeding and energy homeostasis.Molecular psychiatry · 2024Article
- A highly potent, orally bioavailable pyrazole-derived cannabinoid CB2 receptor-selective full agonist forbioRxiv : the preprint server for biology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
39 authors at 8 institutions in 4 countries.
Elliot D MockDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.ORCID http://orcid.org/0000-0002-1500-2856
Mohammed MustafaDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Ozge Gunduz-CinarLaboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA), National Institute of Health (NIH), Bethesda, MD, USA.
Resat CinarLaboratory of Physiologic Studies, NIAAA, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8597-7253
Gavin N PetrieHotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Vasudev KantaeDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Xinyu DiAnalytical Biosciences and Metabolomics, Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
Daisuke OgasawaraDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-2178-4698
Zoltan V VargaLaboratory of Cardiovascular Physiology and Tissue Injury, NIAAA, NIH, Bethesda, MD, USA.
Janos PalocziLaboratory of Cardiovascular Physiology and Tissue Injury, NIAAA, NIH, Bethesda, MD, USA.
Cristina MilianoSchool of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Giulia DonvitoDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Annelot C M van EsbroeckDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.ORCID http://orcid.org/0000-0003-0631-2403
Anouk M F van der GrachtDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Ioli KotsogianniDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Joshua K ParkLaboratory of Physiologic Studies, NIAAA, NIH, Bethesda, MD, USA.
Andrea MartellaDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Tom van der WelDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.ORCID http://orcid.org/0000-0002-6449-3233
Marjolein SoethoudtDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Ming JiangDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Tiemen J WendelDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Antonius P A JanssenDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.ORCID http://orcid.org/0000-0003-4203-261X
Alexander T BakkerDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Colleen M DonovanLaboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA), National Institute of Health (NIH), Bethesda, MD, USA.
Laura I CastilloLaboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA), National Institute of Health (NIH), Bethesda, MD, USA.
Bogdan I FloreaBio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Jesse WatPivot Park Screening Centre B.V., Oss, the Netherlands.
Helma van den HurkPivot Park Screening Centre B.V., Oss, the Netherlands.
Matthias WittwerRoche Innovation Center Basel, F. Hoffman-La Roche Ltd, Basel, Switzerland.
Uwe GretherRoche Innovation Center Basel, F. Hoffman-La Roche Ltd, Basel, Switzerland.
Andrew HolmesLaboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA), National Institute of Health (NIH), Bethesda, MD, USA.
Constant A A van BoeckelDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
Thomas HankemeierAnalytical Biosciences and Metabolomics, Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
Benjamin F CravattDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5330-3492
Matthew W BuczynskiSchool of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Matthew N HillHotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Pal PacherLaboratory of Cardiovascular Physiology and Tissue Injury, NIAAA, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-7036-8108
Aron H LichtmanDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Mario van der SteltDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands. m.van.der.stelt@chem.leidenuniv.nl.ORCID http://orcid.org/0000-0002-1029-5717
Leiden University · NLNational Institutes of Health · USNational Institute on Alcohol Abuse and Alcoholism · USVirginia Commonwealth University · USRoche (Switzerland) · CHScripps Research Institute · USUniversity of Calgary · CAVirginia Tech · US
Funding
Mechanism of oxidative/nitrosative stress and inflammation-induced tissue injuryZIAAA000375 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI PACHER, PAL · 2009 to 2025
$27.8MMOUNT SINAI MEDICAL SCIENTIST TRAINING PROGRAMT32GM007280 · NIGMS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BARON, MARGARET H · 1985 to 2021
$22.8MCHEMOPROTEOMIC METHODS FOR SERINE HYDROLASE INHIBITOR DEVELOPMENTR01DA033760 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI CRAVATT, BENJAMIN F, SCAMPAVIA, LOUIS DANIEL · 2012 to 2021
$5.1MCB1 Allosteric Modulators: Molecular, Cellular and In Vivo PharmacologyR01DA039942 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI KINSEY, STEVEN G., LICHTMAN, ARON H · 2016 to 2020
$2.6MMouse models of the early life origins of stress disordeZ01AA000411 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI HOLMES, ANDREW · 2004 to 2008
$1.9MIntegrated Acoustic Transfer System for HTS Library ManagementS10OD025279 · OD · SCRIPPS FLORIDA · PI SCAMPAVIA, LOUIS DANIEL · 2018 to 2018
$624kHTS Drug Discovery DispensersS10OD026857 · OD · SCRIPPS FLORIDA · PI SCAMPAVIA, LOUIS DANIEL · 2019 to 2019
$452kCIHR FDN-143329Intramural NIH HHS Z01 AA000411NIDA NIH HHS R01 DA033760NIDA NIH HHS R01 DA039942NIGMS NIH HHS T32 GM007280NIH HHS S10 OD025279NIH HHS S10 OD026857
Abstract
N-acylethanolamines (NAEs), which include the endocannabinoid anandamide, represent an important family of signaling lipids in the brain. The lack of chemical probes that modulate NAE biosynthesis in living systems hamper the understanding of the biological role of these lipids. Using a high-throughput screen, chemical proteomics and targeted lipidomics, we report here the discovery and characterization of LEI-401 as a CNS-active N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor. LEI-401 reduced NAE levels in neuroblastoma cells and in the brain of freely moving mice, but not in NAPE-PLD KO cells and mice, respectively. LEI-401 activated the hypothalamus-pituitary-adrenal axis and impaired fear extinction, thereby emulating the effect of a cannabinoid CB
Indexed as
AmidohydrolasesAnimalsBehavior, AnimalBlood ProteinsBrainCannabinoid Receptor AntagonistsCell Line, TumorDrug Evaluation, PreclinicalEnzyme InhibitorsFatty Acid Amide HydrolasesFearHumansLipid MetabolismMaleMiceMice, Inbred C57BLAmidohydrolasesBlood ProteinsCannabinoid Receptor AntagonistsEnzyme InhibitorsFatty Acid Amide HydrolasesN-acylphosphatidylethanolaminePhosphatidylethanolaminesPhospholipase DReceptors, Cannabinoid
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
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.