ArticleBritish journal of pharmacology2012
The ω3-polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A(2) and suppress PGE(2) formation in mesangial cells.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Research progress of cPLA2 in cardiovascular diseases (Review).Molecular medicine reports · 2025Review
- Inhibition of DYRK1B BY C81 impedes inflammatory processes in leukocytes by reducing STAT3 activity.Cellular and molecular life sciences : CMLS · 2025Article
- Functions and mechanisms of cytosolic phospholipase ANeural regeneration research · 2023Review
- Article
- Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes.iScience · 2021Article
- Inhibition of Cytosolic Phospholipase A2α Induces Apoptosis in Multiple Myeloma Cells.Molecules (Basel, Switzerland) · 2021Article
- Arachidonic acid drives adaptive responses to chemotherapy-induced stress in malignant mesothelioma.Journal of experimental & clinical cancer research : CR · 2021Article
- α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin EBiomolecules · 2021Article
- cPLABiomolecules · 2020Article
- Cytosolic Phospholipase A2 Alpha Regulates TLR Signaling and Migration in Metastatic 4T1 Cells.International journal of molecular sciences · 2019Article
- Lipid-metabolizing serine hydrolases in the mammalian central nervous system: endocannabinoids and beyond.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Small-molecule inhibitors as potential therapeutics and as tools to understand the role of phospholipases ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Cytosolic group IVA phospholipase A2 inhibitors, AVX001 and AVX002, ameliorate collagen-induced arthritis.Arthritis research & therapy · 2019Article
- Small Peptides Able to Suppress Prostaglandin E₂ Generation in Renal Mesangial Cells.Molecules (Basel, Switzerland) · 2018Article
- Development of Potent and Selective Inhibitors for Group VIA Calcium-Independent Phospholipase A2 Guided by Molecular Dynamics and Structure-Activity Relationships.Journal of medicinal chemistry · 2016Article
- TNF-α-Induced cPLAFrontiers in pharmacology · 2016Article
- Article
- Cytosolic phospholipase A2 regulates TNF-induced production of joint destructive effectors in synoviocytes.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeω3-polyunsaturated fatty acids (ω3-PUFAs) are known to exert anti-inflammatory effects in various disease models although their direct targets are only poorly characterized. EXPERIMENTAL APPROACH: Here we report on two new cPLA(2) inhibitors, the ω3-derivatives AVX001 and AVX002, and their effects on inflammatory PGE(2) production in cultures of renal mesangial cells. KEY
resultsAVX001 and AVX002 dose-dependently inhibited the group IVA cytosolic phospholipase A(2) (cPLA(2) ) in an in vitro activity assay with similar IC(50) values for AVX001 and AVX002, whereas the known cPLA(2) inhibitor AACOCF(3) was less potent and docosahexaenoic acid (DHA) was inactive. In renal mesangial cells, AVX001 and AVX002 suppressed IL-1β-induced PGE(2) synthesis. Mechanistically, this effect occurred by a down-regulation of IL-1β-induced group IIA-sPLA(2) protein expression, mRNA expression and promoter activity. A similar but less potent effect was seen with AACOCF(3) and no effect was seen with DHA. As gene expression of sPLA(2) is known to be regulated by the transcription factor NF-κB, we further investigated NF-κB activation. Both compounds prevented NF-κB activation by blocking degradation of the inhibitor of κB. CONCLUSIONS AND IMPLICATIONS: These data show for the first time that the novel cPLA(2) inhibitors AVX001 and AVX002 exert an anti-inflammatory effect in cultures of renal mesangial cells and reduce the pro-inflammatory mediator PGE(2) through an inhibitory effect on NF-κB activation. Therefore, these compounds may represent promising novel drugs for the treatment of inflammatory disorders.
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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.