ArticleJournal of medicinal chemistry2011
Discovery of potent and selective inhibitors of human platelet-type 12- lipoxygenase.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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.
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Who cites it
37 citing papers in PubMed, 69 citations in OpenAlex.
- Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications.Cell death & disease · 2024Review
- Structural and Functional Biology of Mammalian ALOX Isoforms with Particular Emphasis on Enzyme Dimerization and Their Allosteric Properties.International journal of molecular sciences · 2024Review
- Synthesis of Bioactive Aminomethylated 8-Hydroxyquinolines via the Modified Mannich Reaction.International journal of molecular sciences · 2023Review
- A 12-lipoxygenase-Gpr31 signaling axis is required for pancreatic organogenesis in the zebrafish.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Eicosanoids and Oxidative Stress in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2020Review
- A maresin 1/RORα/12-lipoxygenase autoregulatory circuit prevents inflammation and progression of nonalcoholic steatohepatitis.The Journal of clinical investigation · 2019Article
- Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.Pharmacology & therapeutics · 2019Review
- Targeting Type 1 Diabetes: Selective Approaches for New Therapies.Biochemistry · 2019Review
- Bioactive lipids and pathological retinal angiogenesis.British journal of pharmacology · 2019Review
- Regulation of platelet function and thrombosis by omega-3 and omega-6 polyunsaturated fatty acids.Prostaglandins & other lipid mediators · 2018Review
- Synthesis and Cytoprotective Characterization of 8-Hydroxyquinoline Betti Products.Molecules (Basel, Switzerland) · 2018Article
- Article
- Molecular mechanisms of nonalcoholic fatty liver disease: Potential role for 12-lipoxygenase.Journal of diabetes and its complications · 2017Review
- First Selective 12-LOX Inhibitor, ML355, Impairs Thrombus Formation and Vessel Occlusion In Vivo With Minimal Effects on Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Lipid peroxidation in cell death.Biochemical and biophysical research communications · 2017Review
- Lipids and immunoinflammatory pathways of beta cell destruction.Diabetologia · 2016Review
- Review
- Cytosolic phospholipase A2 plays a crucial role in ROS/NO signaling during microglial activation through the lipoxygenase pathway.Journal of neuroinflammation · 2015Article
- Minireview: 12-Lipoxygenase and Islet β-Cell Dysfunction in Diabetes.Molecular endocrinology (Baltimore, Md.) · 2015Review
- A high-throughput mass spectrometric assay for discovery of human lipoxygenase inhibitors and allosteric effectors.Analytical biochemistry · 2015Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
We report the discovery of novel small molecule inhibitors of platelet-type 12-human lipoxygenase, which display nanomolar activity against the purified enzyme, using a quantitative high-throughput screen (qHTS) on a library of 153607 compounds. These compounds also exhibit excellent specificity, >50-fold selectivity vs the paralogues, 5-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity vs ovine cyclooxygenase-1 and human cyclooxygenase-2. Kinetic experiments indicate this chemotype is a noncompetitive inhibitor that does not reduce the active site iron. Moreover, chiral HPLC separation of two of the racemic lead molecules revealed a strong preference for the (-)-enantiomers (IC(50) of 0.43 ± 0.04 and 0.38 ± 0.05 μM) compared to the (+)-enantiomers (IC(50) of >25 μM for both), indicating a fine degree of selectivity in the active site due to chiral geometry. In addition, these compounds demonstrate efficacy in cellular models, which underscores their relevance to disease modification.
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What OpenQuestion holds
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.