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1

项与 Abrexa Pharmaceuticals, Inc. 相关的药物

J-147

靶点

5-LOX

作用机制

5-LOX抑制剂

在研机构

The Salk Institute for Biological Studies [+1]

原研机构

The Salk Institute for Biological Studies

在研适应症

急性缺血性卒中 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

1

项与 Abrexa Pharmaceuticals, Inc. 相关的临床试验

NCT03838185 / Completed临床1期

A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Single Ascending Oral Doses of J147 in Healthy Young Volunteers and Healthy Elderly Volunteers

This Phase I clinical study is a randomized, double-blind, placebo-controlled, parallel-design study to thoroughly assess the safety profile and PK properties of J147 in healthy subjects. The study will include single ascending dose (SAD) in healthy young and elderly subjects.

开始日期2019-01-22

申办/合作机构

Abrexa Pharmaceuticals, Inc.

[+1]

100 项与 Abrexa Pharmaceuticals, Inc. 相关的临床结果

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0 项与 Abrexa Pharmaceuticals, Inc. 相关的专利（医药）

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2

项与 Abrexa Pharmaceuticals, Inc. 相关的文献（医药）

2024-01-01·Physiology & Behavior

J147 affects cognition and anxiety after surgery in Zucker rats

Article

作者: Nabben, M ; Villafranca, J E ; van Leeuwen, B L ; Schoemaker, R G ; Oberman, K

Vulnerable patients are at risk for neuroinflammation-mediated post-operative complications, including depression (POD) and cognitive dysfunction (POCD). Zucker rats, expressing multiple risk factors for post-operative complications in humans, may provide a clinically relevant model to study pathophysiology and explore potential interventions. J147, a newly developed anti-dementia drug, was shown to prevent POCD in young healthy rats, and improved early post-surgical recovery in Zucker rats. Aim of the present study was to investigate POCD and the therapeutic potential of J147 in male Zucker rats. Risk factors in the Zucker rat strain were evaluated by comparison with lean littermates. Zucker rats were subjected to major abdominal surgery. Acute J147 treatment was provided by a single iv injection (10 mg/kg) at the start of surgery, while chronic J147 treatment was provided in the food (aimed at 30 mg/kg/day), starting one week before surgery and up to end of protocol. Effects on behavior were assessed, and plasma, urine and brain tissue were collected and processed for immunohistochemistry and molecular analyses. Indeed, Zucker rats displayed increased risk factors for POCD, including obesity, high plasma triglycerides, low grade systemic inflammation, impaired spatial learning and decreased neurogenesis. Surgery in Zucker rats reduced exploration and increased anxiety in the Open Field test, impaired short-term spatial memory, induced a shift in circadian rhythm and increased plasma neutrophil gelatinase-associated lipocalin (NGAL), microglia activity in the CA1 and blood brain barrier leakage. Chronic, but not acute J147 treatment reduced anxiety in the Open Field test and protected against the spatial memory decline. Moreover, chronic J147 increased glucose sensitivity. Acute J147 treatment improved long-term spatial memory and reversed the circadian rhythm shift. No anti-inflammatory effects were seen for J147. Although Zucker rats displayed risk factors, surgery did not induce extensive POCD. However, increased anxiety may indicate POD. Treatment with J147 showed positive effects on behavioral and metabolic parameters, but did not affect (neuro)inflammation. The mixed effect of acute and chronic treatment may suggest a combination for optimal treatment.

Frontiers in Neurology3区 · 医学

J147 Reduces tPA-Induced Brain Hemorrhage in Acute Experimental Stroke in Rats

3区 · 医学

ArticleOA

作者: Villafranca, J Ernest ; Wang, Min ; Zhong, Wei ; Jin, Rong ; Li, Guohong ; Kissinger, Charles R

Background and purposeJ147, a novel neurotrophic compound, was originally developed to treat aging-associated neurological diseases. Based on the broad spectrum of cytoprotective effects exhibited by this compound, we investigated whether J147 has cerebroprotection for acute ischemic stroke and whether it can enhance the effectiveness of thrombolytic therapy with tissue plasminogen activator (tPA).MethodsRats were subjected to transient occlusion of the middle cerebral artery (tMCAO) by insertion of an intraluminal suture or embolic middle cerebral artery occlusion (eMCAO), and treated intravenously with J147 alone or in combination with tPA.ResultsWe found that J147 treatment significantly reduced infarct volume when administered at 2 h after stroke onset in the tMCAO model, but had no effect in eMCAO without tPA. However, combination treatment with J147 plus tPA at 4 h after stroke onset significantly reduced infarct volume and neurological deficits at 72 h after stroke compared with saline or tPA alone groups in the eMCAO model. Importantly, the combination treatment significantly reduced delayed tPA-associated brain hemorrhage and secondary microvascular thrombosis. These protective effects were associated with J147-mediated inhibition of matrix metalloproteinase-9 (MMP9), 15-lipoxygenase-1, and plasminogen activator inhibitor (PAI) expression in the ischemic hemispheres (predominantly in ischemic cerebral endothelium). Moreover, the combination treatment significantly reduced circulating platelet activation and platelet-leukocyte aggregation compared with saline or tPA alone groups at 24 h after stroke, which might also contribute to reduced microvascular thrombosis and neuroinflammation (as demonstrated by reduced neutrophil brain infiltration and microglial activation).ConclusionOur results demonstrate that J147 treatment alone exerts cerebral cytoprotective effects in a suture model of acute ischemic stroke, while in an embolic stroke model co-administration of J147 with tPA reduces delayed tPA-induced intracerebral hemorrhage and confers cerebroprotection. These findings suggest that J147-tPA combination therapy could be a promising approach to improving the treatment of ischemic stroke.

100 项与 Abrexa Pharmaceuticals, Inc. 相关的药物交易

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100 项与 Abrexa Pharmaceuticals, Inc. 相关的转化医学

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