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Furoxans as Novel Therapeutics for Neurodegenerative Disorders

詳細技術說明

Project ID:  D2017-15 Invention Description:Nitric oxide (NO) signaling is essential for brain activity and normal neuronal function. Disrupted NO signaling is implicated in several central nervous system (CNS) and neurodegenerative disorders. NO mimetics, such as nitrates, have been implicated for use against a variety of neurological disorders, including stroke, depression, and Alzheimer’s disease. This is due to the ability of the nitrates to enhance NO-related signaling. Unfortunately, development of nitrates for neurodegenerative disorders has faced several challenges, such as poor metabolic stability, an inability to effectively monitor the level of the nitrates, and formulation instability in the presence of atmospheric humidity. Researchers at the University of Toledo have designed and synthesized novel furoxans that are orally bioavailable in the brain and are capable of enhancing in vivo cognition.  Applications: •       The designed and synthesized novel furoxans may be used for treating multiple neurodegenerative disorders, including Alzheimer’s disease (AD), stroke, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE)•       The furoxans may be used to reverse memory impairment in patients•       The furoxans may be used to provide neuroprotective and neuro-restorative effects following incidences of acute neuronal insults such as concussions and stroke Value Proposition: •       These furoxans are distinct from previous molecules based on a unique understanding of furoxan mechanistic reactivity, experience in NO mimetic CNS drug discovery, and data reporting in vivo furoxan efficacy in relevant preclinical animal models of memory and neurodegeneration.•       Novel findings include in vivo cognition enhancement (memory improvement) and in vivo neuro-restorative effects in a stroke model•       The furoxans exhibited brain bioavailability with enhanced memory improvement and neuroprotective activity in a cellular model of ischemia•       Novel furoxans were synthesized using a novel, scalable synthetic route •       The compounds exhibit appropriate physiochemical properties, based on novel well-defined design criteria, to produce favorable CNS penetration. •       In vitro and in vivo data is available, including data related to target pathway engagement (pharmacodynamics) and pharmacokinetics IP Status: Provisional patent filed

*Abstract

*Principal Investigation

Name: Isaac Schiefer, Assistant Professor

Department: Medicinal and Biological Chemistry

Name: Zahoor Shah, Associate Professor

Department: Pharm-Med/Bio Chem

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美國