ArticleScientific reports2022
Inhibition of interferon-gamma-stimulated melanoma progression by targeting neuronal nitric oxide synthase (nNOS).
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Differentiation state affects PD-L1 expression in cutaneous melanoma: a systematic review.Cellular & molecular biology letters · 2026Pooled it
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- S-nitrosylation topology in melanoma: established mechanisms, unresolved redox-immune links, and a testable framework.Redox biology · 2026Review
- Enhancement of Potency and Selectivity of 2-Aminoquinoline-Based Human Neuronal Nitric Oxide Synthase Inhibitors.Journal of medicinal chemistry · 2026Article
- Potent, Selective, and Brain Penetrant Ether-Linked 2-Aminopyridine Inhibitors of Human Neuronal Nitric Oxide Synthase with Excellent Oral Bioavailability.Journal of medicinal chemistry · 2026Article
- New Inhibitors of Neuronal Nitric Oxide Synthase for the Treatment of Melanoma.Journal of medicinal chemistry · 2026Article
- S-nitrosylation of IRF7 induced by NOS1 expression in melanoma suppresses anti-tumor immunity.Cell death & disease · 2026Article
- Dynamic tail amine interactions drive isoform selectivity for potent human neuronal nitric oxide synthase inhibitors.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Dissecting Melanoma Ecosystem Heterogeneity from Molecular Characteristics to Genetic Variation at Single-Cell Resolution.International journal of molecular sciences · 2025Article
- Truncated pyridinylbenzylamines: Potent, selective, and highly membrane permeable inhibitors of human neuronal nitric oxide synthase.Bioorganic & medicinal chemistry · 2025Article
- Modulation of heme peroxo nucleophilicities with axial ligands reveal key insights into the mechanistic landscape of nitric oxide synthase.Chemical science · 2025Article
- Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors.Pharmaceutics · 2025Article
- Dual role of interferon-gamma in the response of melanoma patients to immunotherapy with immune checkpoint inhibitors.Molecular cancer · 2025Review
- Crosstalk Between nNOS/NO and COX-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression.Cancers · 2025Article
- Modulation of MHC expression by interferon-gamma and its influence on PBMC-mediated cytotoxicity in canine mast cell tumour cells.Scientific reports · 2024Article
- Article
- Investigation of tryptophan to kynurenine degradation in response to interferon-γ in melanoma cell lines.Biochemistry and biophysics reports · 2024Article
- Improved synthesis and anticancer activity of a potent neuronal nitric oxide synthase inhibitor.Bioorganic & medicinal chemistry letters · 2023Article
- ULK1 Depletion Protects Mice from Diethylnitrosamine-Induced Hepatocarcinogenesis by Promoting Apoptosis and Inhibiting Autophagy.Journal of hepatocellular carcinoma · 2023Article
- HLA-DR expression in melanoma: from misleading therapeutic target to potential immunotherapy biomarker.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Interferon-gamma (IFN-γ) is shown to stimulate melanoma development and progression. However, the underlying mechanism has not been completely defined. Our study aimed to determine the role of neuronal nitric oxide synthase (nNOS)-mediated signaling in IFN-γ-stimulated melanoma progression and the anti-melanoma effects of novel nNOS inhibitors. Our study shows that IFN-γ markedly induced the expression levels of nNOS in melanoma cells associated with increased intracellular nitric oxide (NO) levels. Co-treatment with novel nNOS inhibitors effectively alleviated IFN-γ-activated STAT1/3. Further, reverse phase protein array (RPPA) analysis demonstrated that IFN-γ induced the expression of HIF1α, c-Myc, and programmed death-ligand 1 (PD-L1), in contrast to IFN-α. Blocking the nNOS-mediated signaling pathway using nNOS-selective inhibitors was shown to effectively diminish IFN-γ-induced PD-L1 expression in melanoma cells. Using a human melanoma xenograft mouse model, the in vivo studies revealed that IFN-γ increased tumor growth compared to control, which was inhibited by the co-administration of nNOS inhibitor MAC-3-190. Another nNOS inhibitor, HH044, was shown to effectively inhibit in vivo tumor growth and was associated with reduced PD-L1 expression levels in melanoma xenografts. Our study demonstrates the important role of nNOS-mediated NO signaling in IFN-γ-stimulated melanoma progression. Targeting nNOS using highly selective small molecular inhibitors is a unique and effective strategy to improve melanoma treatment.
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Registered trials
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