ArticleJournal of medicinal chemistry2014
Synthesis and structure-activity relationship studies of 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase.
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 42 papers.
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Who cites it
42 citing papers in PubMed, 86 citations in OpenAlex.
- Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12.Nature communications · 2026Article
- Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target.Molecular biomedicine · 2026Review
- Platelet activation, aspirin, and cancer: From basic science to clinical trials.Pharmacological reviews · 2026Review
- Emerging Targets, Novel Directions, and Innovative Approaches in Thrombosis Therapy.Aging and disease · 2025Review
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.JCI insight · 2024Article
- Structural and Functional Biology of Mammalian ALOX Isoforms with Particular Emphasis on Enzyme Dimerization and Their Allosteric Properties.International journal of molecular sciences · 2024Review
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.bioRxiv : the preprint server for biology · 2024Article
- Mechanism of Bile Acid in Regulating Platelet Function and Thrombotic Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Platelets as crucial players in the dynamic interplay of inflammation, immunity, and cancer: unveiling new strategies for cancer prevention.Frontiers in pharmacology · 2024Review
- Cryo-EM structures of human arachidonate 12S-lipoxygenase bound to endogenous and exogenous inhibitors.Blood · 2023Article
- Pass the 12-LOX!Blood · 2023Article
- Targeting ferroptosis opens new avenues for the development of novel therapeutics.Signal transduction and targeted therapy · 2023Review
- Membrane Lipid Derivatives: Roles of Arachidonic Acid and Its Metabolites in Pancreatic Physiology and Pathophysiology.Molecules (Basel, Switzerland) · 2023Review
- Biochemical and hydrogen-deuterium exchange studies of the single nucleotide polymorphism Y649C in human platelet 12-lipoxygenase linked to a bleeding disorder.Archives of biochemistry and biophysics · 2023Article
- Activation of ALOX12 by a multi-organelle-orienting photosensitizer drives ACSL4-independent cell ferroptosis.Cell death & disease · 2022Article
- ML355 Modulates Platelet Activation and Prevents ABT-737 Induced Apoptosis in Platelets.The Journal of pharmacology and experimental therapeutics · 2022Article
- Synthetic high-density lipoproteins loaded with an antiplatelet drug for efficient inhibition of thrombosis in mice.Science advances · 2020Article
- Fatty Acid Allosteric Regulation of C-H Activation in Plant and Animal Lipoxygenases.Molecules (Basel, Switzerland) · 2020Review
- Design and Development of Novel Urea, Sulfonyltriurea, and Sulfonamide Derivatives as Potential Inhibitors ofPharmaceuticals (Basel, Switzerland) · 2020Article
- Biosynthesis of the Maresin Intermediate, 13S,14S-Epoxy-DHA, by Human 15-Lipoxygenase and 12-Lipoxygenase and Its Regulation through Negative Allosteric Modulators.Biochemistry · 2020Article
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Human lipoxygenases (LOXs) are a family of iron-containing enzymes which catalyze the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Our group has taken a particular interest in platelet-type 12-(S)-LOX (12-LOX) because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Herein, we report the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. Top compounds, exemplified by 35 and 36, display nM potency against 12-LOX, excellent selectivity over related lipoxygenases and cyclooxygenases, and possess favorable ADME properties. In addition, both compounds inhibit PAR-4 induced aggregation and calcium mobilization in human platelets and reduce 12-HETE in β-cells.
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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.