ArticleNeuroscience2019
Functionalized Phenylbenzamides Inhibit Aquaporin-4 Reducing Cerebral Edema and Improving Outcome in Two Models of CNS Injury.
Article in Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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
34 citing papers in PubMed.
- How is rosette formation in brain tumours linked with cerebrospinal fluid spread?Brain tumor pathology · 2026Review
- Emerging Roles of Meningeal Lymphatic Vessels in Ischemic Stroke.Molecular neurobiology · 2025Review
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- Aquaporins in Acute Brain Injury: Insights from Clinical and Experimental Studies.Biomedicines · 2025Review
- Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation.Inflammation · 2025Article
- Exploring Aquaporins in Human Studies: Mechanisms and Therapeutic Potential in Critical Illness.Life (Basel, Switzerland) · 2024Review
- Article
- Aquaporins: Gatekeepers of Fluid Dynamics in Traumatic Brain Injury.International journal of molecular sciences · 2024Review
- Article
- Toward New AQP4 Inhibitors: ORI-TRN-002.International journal of molecular sciences · 2024Article
- Aquaporins in sepsis- an update.Frontiers in immunology · 2024Review
- Effects of CFTR-ENaC on spinal cord edema after spinal cord injury.Open medicine (Warsaw, Poland) · 2024Article
- New Insights on Mechanisms and Therapeutic Targets of Cerebral Edema.Current neuropharmacology · 2024Review
- Blood-Brain Barrier Breakdown in Alzheimer's Disease: Mechanisms and Targeted Strategies.International journal of molecular sciences · 2023Review
- Article
- Cation flux through SUR1-TRPM4 and NCX1 in astrocyte endfeet induces water influx through AQP4 and brain swelling after ischemic stroke.Science signaling · 2023Article
- Water channel aquaporin 4 is required for T cell receptor mediated lymphocyte activation.Journal of leukocyte biology · 2023Article
- T cells go with the flow: aquaporin 4 is required for full T-cell activation.Journal of leukocyte biology · 2023Article
- The lymphatic drainage systems in the brain: a novel target for ischemic stroke?Neural regeneration research · 2023Review
- Endothelial Dysfunction in Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Cerebral edema in ischemic stroke can lead to increased intracranial pressure, reduced cerebral blood flow and neuronal death. Unfortunately, current therapies for cerebral edema are either ineffective or highly invasive. During the development of cytotoxic and subsequent ionic cerebral edema water enters the brain by moving across an intact blood brain barrier and through aquaporin-4 (AQP4) at astrocyte endfeet. Using AQP4-expressing cells, we screened small molecule libraries for inhibitors that reduce AQP4-mediated water permeability. Additional functional assays were used to validate AQP4 inhibition and identified a promising structural series for medicinal chemistry. These efforts improved potency and revealed a compound we designated AER-270, N-[3,5-bis (trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide. AER-270 and a prodrug with enhanced solubility, AER-271 2-{[3,5-Bis(trifluoromethyl) phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, improved neurological outcome and reduced swelling in two models of CNS injury complicated by cerebral edema: water intoxication and ischemic stroke modeled by middle cerebral artery occlusion.
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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.