ArticleJournal of medicinal chemistry2015
Rational Development of a Potent 15-Lipoxygenase-1 Inhibitor with in Vitro and ex Vivo Anti-inflammatory Properties.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
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Who cites it
25 citing papers in PubMed.
- Light-Controlled Modulation of 15-Lipoxygenase-1 Regulates Intestinal Inflammatory Signaling.Angewandte Chemie (International ed. in English) · 2026Article
- The Evolution of Fluorescein into A Potential Theranostic Tool.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Crafting Molecular Tools for 15-Lipoxygenase-1 in a Single Step.Angewandte Chemie (International ed. in English) · 2025Article
- Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide.Beilstein journal of organic chemistry · 2025Article
- Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications.Cell death & disease · 2024Review
- Synthesis of new multitarget-directed ligands containing thienopyrimidine nucleus for inhibition of 15-lipoxygenase, cyclooxygenases, and pro-inflammatory cytokines.European journal of medicinal chemistry · 2023Article
- Different Structures-Similar Effect: Do Substituted 5-(4-Methoxyphenyl)-1Molecules (Basel, Switzerland) · 2023Article
- Synthesis, Biological Evaluation, and Molecular Dynamics of Carbothioamides Derivatives as Carbonic Anhydrase II and 15-Lipoxygenase Inhibitors.Molecules (Basel, Switzerland) · 2022Article
- 4-Chlorophenyl-ACS omega · 2022Article
- Investigating the effects of two novel 4-MMPB analogs as potent lipoxygenase inhibitors for prostate cancer treatment.Journal of biological research (Thessalonike, Greece) · 2021Article
- Catalytic enantioselective addition of organometallics to unprotected carboxylic acids.Nature communications · 2019Article
- Novel 15-Lipoxygenase-1 Inhibitor Protects Macrophages from Lipopolysaccharide-Induced Cytotoxicity.Journal of medicinal chemistry · 2019Article
- Replacement of an Indole Scaffold Targeting Human 15-Lipoxygenase-1 Using Combinatorial Chemistry.Helvetica chimica acta · 2019Article
- Review
- Comparison of eight 15-lipoxygenase (LO) inhibitors on the biosynthesis of 15-LO metabolites by human neutrophils and eosinophils.PloS one · 2018Article
- A 6-alkylsalicylate histone acetyltransferase inhibitor inhibits histone acetylation and pro-inflammatory gene expression in murine precision-cut lung slices.Pulmonary pharmacology & therapeutics · 2017Article
- HDAC1-3 inhibitor MS-275 enhances IL10 expression in RAW264.7 macrophages and reduces cigarette smoke-induced airway inflammation in mice.Scientific reports · 2017Article
- Lipid peroxidation in cell death.Biochemical and biophysical research communications · 2017Review
- Lipoxygenase Activity Accelerates Programmed Spore Germination inFrontiers in microbiology · 2017Article
- Human 15-LOX-1 active site mutations alter inhibitor binding and decrease potency.Bioorganic & medicinal chemistry · 2016Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Human 15-lipoxygenase-1 (h-15-LOX-1) is a mammalian lipoxygenase and plays an important role in several inflammatory lung diseases such as asthma, COPD, and chronic bronchitis. Novel potent inhibitors of h-15-LOX-1 are required to explore the role of this enzyme further and to enable drug discovery efforts. In this study, we applied an approach in which we screened a fragment collection that is focused on a diverse substitution pattern of nitrogen-containing heterocycles such as indoles, quinolones, pyrazoles, and others. We denoted this approach substitution-oriented fragment screening (SOS) because it focuses on the identification of novel substitution patterns rather than on novel scaffolds. This approach enabled the identification of hits with good potency and clear structure-activity relationships (SAR) for h-1-5-LOX-1 inhibition. Molecular modeling enabled the rationalization of the observed SAR and supported structure-based design for further optimization to obtain inhibitor 14 d that binds with a Ki of 36 nM to the enzyme. In vitro and ex vivo biological evaluations of our best inhibitor demonstrate a significant increase of interleukin-10 (IL-10) gene expression, which indicates its anti-inflammatory properties.
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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.