ArticlePharmacology research & perspectives2016
Gastrointestinal safety, chemotherapeutic potential, and classic pharmacological profile of NOSH-naproxen (AVT-219) a dual NO- and H2S-releasing hybrid.
Article in Pharmacology research & perspectives, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- Inhibition of hepatic gluconeogenesis in type 2 diabetes by metformin: complementary role of nitric oxide.Medical gas research · 2025Review
- The Triple Crown: NO, CO, and HPharmacology & therapeutics · 2023Review
- Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies.Redox biology · 2023Review
- Signaling pathways in cutaneous wound healing.Frontiers in physiology · 2022Review
- Anticancer and Anti-Inflammatory Mechanisms of NOSH-Aspirin and Its Biological Effects.Computational and mathematical methods in medicine · 2022Review
- Article
- Gaseous Mediators as a Key Molecular Targets for the Development of Gastrointestinal-Safe Anti-Inflammatory Pharmacology.Frontiers in pharmacology · 2021Review
- The evolving landscape for cellular nitric oxide and hydrogen sulfide delivery systems: A new era of customized medications.Biochemical pharmacology · 2020Review
- Chemoprevention of Colorectal Cancer.Gastroenterology · 2020Review
- Discovery and Development of a Novel mPGES-1/5-LOX Dual Inhibitor LFA-9 for Prevention and Treatment of Chronic Inflammatory Diseases.Journal of inflammation research · 2020Article
- S-nitrosothiols and HRedox biology · 2019Review
- Effects of Hydrogen Sulfide on Carbohydrate Metabolism in Obese Type 2 Diabetic Rats.Molecules (Basel, Switzerland) · 2019Article
- Clinically Relevant Anti-Inflammatory Agents for Chemoprevention of Colorectal Cancer: New Perspectives.International journal of molecular sciences · 2018Review
- Indole Derivatives as Cyclooxygenase Inhibitors: Synthesis, Biological Evaluation and Docking Studies.Molecules (Basel, Switzerland) · 2018Article
- The dichotomous role of HBiochemical pharmacology · 2018Review
- Synthesis, crystallographic characterization, molecular docking and biological activity of isoquinoline derivatives.Chemistry Central journal · 2017Article
- A novel pH-controlled hydrogen sulfide donor protects gastric mucosa from aspirin-induced injury.Journal of cellular and molecular medicine · 2017Article
- Gastrointestinal safety, chemotherapeutic potential, and classic pharmacological profile of NOSH-naproxen (AVT-219) a dual NO- and H2S-releasing hybrid.Pharmacology research & perspectives · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Naproxen (NAP) is a potent nonsteroidal anti-inflammatory drug (NSAID) with a favorable cardiovascular profile. However, its long-term use may lead to serious gastrointestinal and renal side effects. NOSH- (nitric oxide and hydrogen sulfide) releasing naproxen (NOSH-NAP, AVT-219) belongs to a new class of anti-inflammatory agents designed to overcome these limitations. We compared the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, and antiplatelet properties of AVT-219 to that of NAP in preclinical animal models. We also evaluated its anticancer effects in 11 human cancer cell (HCC) lines of six different tissue origins and in a chemotherapeutic xenograft mouse model of colon cancer. AVT-219: (1) was orders of magnitude more potent than NAP in inhibiting the growth of cultured HCC; (2) was safe to the stomach, whereas NAP caused significant ulceration; (3) showed strong anti-inflammatory, analgesic, antipyretic, and antiplatelet properties comparable to NAP; and (4) NAP caused a significant rise in plasma tumor necrosis factor-alpha (TNFα), whereas in the AVT-219-treated rats this rise was significantly less. Mechanistically, AVT-219 was a strong antioxidant, inhibited cyclooxygenase (COX)-1 and -2, thus reducing prostaglandin (PG) E2. In xenografts, AVT-219 significantly reduced tumor growth and tumor mass with no sign of GI toxicity, whereas NAP-treated mice died due to GI bleeding. AVT-219 displayed considerable safety and potency in inhibiting HCC growth; was an effective analgesic, antipyretic, antiplatelet, and anti-inflammatory; and was significantly more efficacious than NAP in reducing the growth of established tumors in a xenograft mouse model.
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Registered trials
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