ArticleJournal of medicinal chemistry2010
Design, synthesis, and biological evaluation of halogenated N-(2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: discovery of an isoform-selective small molecule phospholipase D2 inhibitor.
Article in Journal of medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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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
63 citing papers in PubMed, 90 citations in OpenAlex.
- Phospholipase D2 acts upstream of PI4P 5-kinases in the response of neurons to extracellular viscosity.iScience · 2026Article
- Article
- Exosome-Mediated Delivery of a PLD1 Modulator Overcomes Bioavailability Hurdles to Target Synaptopathy in Neurodegenerative Diseases.Pharmaceutical research · 2025Article
- PLD1 is a key player in cancer stemness and chemoresistance: Therapeutic targeting of cross-talk between the PI3K/Akt and Wnt/β-catenin pathways.Experimental & molecular medicine · 2024Review
- Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration.International journal of molecular sciences · 2023Article
- Parkin coordinates mitochondrial lipid remodeling to execute mitophagy.EMBO reports · 2022Article
- Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy.The Journal of clinical investigation · 2021Article
- Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus.Cellular and molecular life sciences : CMLS · 2021Article
- Enhancement in Phospholipase D Activity as a New Proposed Molecular Mechanism of Haloperidol-Induced Neurotoxicity.International journal of molecular sciences · 2020Article
- Dopamine receptors in emesis: Molecular mechanisms and potential therapeutic function.Pharmacological research · 2020Review
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Human PLD structures enable drug design and characterization of isoenzyme selectivity.Nature chemical biology · 2020Article
- Crystal structure of plant PLDα1 reveals catalytic and regulatory mechanisms of eukaryotic phospholipase D.Cell research · 2020Article
- IMPACT: Imaging phospholipase d activity with clickable alcohols via transphosphatidylation.Methods in enzymology · 2020Article
- Phospholipase D and Choline Metabolism.Handbook of experimental pharmacology · 2020Review
- Suppressing aberrant phospholipase D1 signaling in 3xTg Alzheimer's disease mouse model promotes synaptic resilience.Scientific reports · 2019Article
- Phospholipase D2 in prostate cancer: protein expression changes with Gleason score.British journal of cancer · 2019Article
- A real-time, click chemistry imaging approach reveals stimulus-specific subcellular locations of phospholipase D activity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Role of phospholipase D in migration and invasion induced by linoleic acid in breast cancer cells.Molecular and cellular biochemistry · 2019Article
- Preparation and Evaluation of Liposomes Co-Loaded with Doxorubicin, Phospholipase D Inhibitor 5-Fluoro-2-Indolyl Deschlorohalopemide (FIPI) and D-Alpha Tocopheryl Acid Succinate (α-TOS) for Anti-Metastasis.Nanoscale research letters · 2019Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Phospholipase D (PLD) catalyzes the conversion of phosphatidylcholine to the lipid second messenger phosphatidic acid. Two mammalian isoforms of PLD have been identified, PLD1 and PLD2, which share 53% sequence identity and are subject to different regulatory mechanisms. Inhibition of PLD enzymatic activity leads to increased cancer cell apoptosis, decreased cancer cell invasion, and decreased metastasis of cancer cells; therefore, the development of isoform-specific, PLD inhibitors is a novel approach for the treatment of cancer. Previously, we developed potent dual PLD1/PLD2, PLD1-specific (>1700-fold selective), and moderately PLD2-preferring (>10-fold preferring) inhibitors. Here, we describe a matrix library strategy that afforded the most potent (PLD2 IC(50) = 20 nM) and selective (75-fold selective versus PLD1) PLD2 inhibitor to date, N-(2-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)-2-naphthamide (22a), with an acceptable DMPK profile. Thus, these new isoform-selective PLD inhibitors will enable researchers to dissect the signaling roles and therapeutic potential of individual PLD isoforms to an unprecedented degree.
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Registered trials
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.