ArticleNeuroscience letters2016
A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia-reperfusion injury in mice.
Article in Neuroscience letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Therapeutic potential of nitric oxide and its donors in hemorrhagic and ischemic stroke: a systematic review.Medical gas research · 2026Pooled it
- Chemistry and Biological Activity of 11Molecules (Basel, Switzerland) · 2026Review
- Neuroprotective and Antioxidant Properties of Different Novel Steroid-Derived Nitrones and Oximes on Cerebral Ischemia In Vitro.International journal of molecular sciences · 2025Article
- c-Jun N-Terminal Kinase (JNK) Inhibitor IQ-1S as a Suppressor of Tumor Spheroid Growth.Molecules (Basel, Switzerland) · 2025Article
- Local arterial administration of acidified malonate as an adjunct therapy to mechanical thrombectomy in ischemic stroke.Cardiovascular research · 2025Article
- Article
- Regulation of Blood-Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer's Disease and Brain Tumors.Molecules (Basel, Switzerland) · 2025Review
- Evaluation of Nitric Oxide-Donating Properties of 11Molecules (Basel, Switzerland) · 2024Article
- Pharmacokinetics of a New Neuroprotector - Indenoquinoxalinone Derivative after Intravenous Administration in Rabbits and Rats.Bulletin of experimental biology and medicine · 2023Article
- Neuroprotective Effects of Tryptanthrin-6-Oxime in a Rat Model of Transient Focal Cerebral Ischemia.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Experimental and Computational Investigation of the Oxime Bond Stereochemistry in c-Jun N-terminal Kinase 3 Inhibitors 11Pharmaceutics · 2023Article
- Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1S.Biomedicines · 2023Article
- Neuroprotective Effects of the Lithium Salt of a Novel JNK Inhibitor in an Animal Model of Cerebral Ischemia-Reperfusion.Biomedicines · 2022Article
- Modified middle cerebral artery occlusion model provides detailed intraoperative cerebral blood flow registration and improves neurobehavioral evaluation.Journal of neuroscience methods · 2021Article
- Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential.Biomolecules · 2021Review
- Acorus tatarinowii Schott extract reduces cerebral edema caused by ischemia-reperfusion injury in rats: involvement in regulation of astrocytic NKCC1/AQP4 and JNK/iNOS-mediated signaling.BMC complementary medicine and therapies · 2020Article
- Review
- Antihypertensive activity of a new c-Jun N-terminal kinase inhibitor in spontaneously hypertensive rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Article
- Article
- Arene-Ruthenium(II) Complexes Containing 11ACS omega · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The c-Jun N-terminal kinase (JNK) has been shown to be an important regulator of neuronal cell death. Previously, we synthesized the sodium salt of 11H-indeno[1,2-b]quinoxalin-11-one (IQ-1S) and demonstrated that it was a high-affinity inhibitor of the JNK family. In the present work, we found that IQ-1S could release nitric oxide (NO) during its enzymatic metabolism by liver microsomes. Moreover, serum nitrite/nitrate concentration in mice increased after intraperitoneal injection of IQ-1S. Because of these dual actions as JNK inhibitor and NO-donor, the therapeutic potential of IQ-1S was evaluated in an animal stroke model. We subjected wild-type C57BL6 mice to focal ischemia (30min) with subsequent reperfusion (48h). Mice were treated with IQ-1S (25mg/kg) suspended in 10% solutol or with vehicle alone 30min before and 24h after middle cerebral artery (MCA) occlusion (MCAO). Using laser-Doppler flowmetry, we monitored cerebral blood flow (CBF) above the MCA during 30min of MCAO provoked by a filament and during the first 30min of subsequent reperfusion. In mice treated with IQ-1S, ischemic and reperfusion values of CBF were not different from vehicle-treated mice. However, IQ-1S treated mice demonstrated markedly reduced neurological deficit and infarct volumes as compared with vehicle-treated mice after 48h of reperfusion. Our results indicate that the novel JNK inhibitor releases NO during its oxidoreductive bioconversion and improves stroke outcome in a mouse model of cerebral reperfusion. We conclude that IQ-1S is a promising dual functional agent for the treatment of cerebral ischemia and reperfusion injury.
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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 Socratic graph.