ArticleJournal of medicinal chemistry2014
Potent and selective inhibitors of human reticulocyte 12/15-lipoxygenase as anti-stroke therapies.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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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
46 citing papers in PubMed, 92 citations in OpenAlex.
- Lipoxygenase (LOX) signaling in epilepsy: Pathophysiology and therapeutic prospects.Neurobiology of disease · 2026Review
- Light-Controlled Modulation of 15-Lipoxygenase-1 Regulates Intestinal Inflammatory Signaling.Angewandte Chemie (International ed. in English) · 2026Article
- Lipid Metabolism in Central Nervous System Diseases: Pathological Mechanisms and Therapeutic Advances.CNS neuroscience & therapeutics · 2026Review
- Status epilepticus-induced 12/15-lipoxygenase drives neuroinflammation and contributes to neuronal injuries and behavioral comorbidities.Acta pharmacologica Sinica · 2026Article
- 12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi After Subarachnoid Hemorrhage in Mice.Translational stroke research · 2025Article
- Exercise-Stimulated Resolvin Biosynthesis in the Adipose Tissue Is Abrogated by High-Fat Diet-Induced Adrenergic Deficiency.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Inhibition of 12/15-lipoxygenase reduces orthodontically induced root resorption in rats.The Angle orthodontist · 2024Article
- 12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi after Subarachnoid Hemorrhage in Mice.Research square · 2024Article
- The relationship of redox signaling with the risk for atherosclerosis.Frontiers in pharmacology · 2024Review
- Different Structures-Similar Effect: Do Substituted 5-(4-Methoxyphenyl)-1Molecules (Basel, Switzerland) · 2023Article
- A review on the relationship between Arachidonic acid 15-Lipoxygenase (ALOX15) and diabetes mellitus.PeerJ · 2023Review
- 12/15-lipoxygenase inhibition attenuates neuroinflammation by suppressing inflammasomes.Frontiers in cellular neuroscience · 2023Article
- Reevaluation of a Bicyclic Pyrazoline as a Selective 15-Lipoxygenase V-Type Activator Possessing Fatty Acid Specificity.ACS omega · 2022Article
- The role of procoagulant phospholipids on the surface of circulating blood cells in thrombosis and haemostasis.Open biology · 2022Review
- Lipoxygenase inhibitor ML351 dysregulated an innate inflammatory response leading to impaired cardiac repair in acute heart failure.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Gigantol ameliorates CClScientific reports · 2020Article
- Using the Oxytosis/Ferroptosis Pathway to Understand and Treat Age-Associated Neurodegenerative Diseases.Cell chemical biology · 2020Review
- Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Fatty Acid Allosteric Regulation of C-H Activation in Plant and Animal Lipoxygenases.Molecules (Basel, Switzerland) · 2020Review
- Motor deficit in the mouse ferric chloride-induced distal middle cerebral artery occlusion model of stroke.Behavioural brain research · 2020Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
A key challenge facing drug discovery today is variability of the drug target between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes to ischemic brain injury, but its human and rodent isozymes have different inhibitor specificities. In the current work, we have utilized a quantitative high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype for 12/15-LOX inhibition that has nanomolar potency (IC50 = 200 nM) against human 12/15-LOX and is protective against oxidative glutamate toxicity in mouse neuronal HT22 cells. In addition, it exhibited greater than 250-fold selectivity versus related LOX isozymes, was a mixed inhibitor, and did not reduce the active-site ferric ion. Lastly, 1 significantly reduced infarct size following permanent focal ischemia in a mouse model of ischemic stroke. As such, this represents the first report of a selective inhibitor of human 12/15-LOX with demonstrated in vivo activity in proof-of-concept mouse models of stroke.
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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.