Arundic acid(Arundic acid) - 药物靶点：COX-2 x Free radicals x NOS2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(2R)-2-propyloctanoic acid、Arocyte Injection、Arundic acid (JAN/INN)

+ [7]

靶点

COX-2 x Free radicals x NOS2

作用机制

COX-2抑制剂(环氧化酶-2抑制剂)、自由基抑制剂、NOS2抑制剂(诱导型一氧化氮合酶抑制剂)

治疗领域

神经系统疾病心血管疾病内分泌与代谢疾病+ [2]

在研适应症-

非在研适应症

急性缺血性卒中阿尔茨海默症肌萎缩侧索硬化+ [4]

原研机构

Ono Pharmaceutical Co., Ltd.

在研机构-

非在研机构

Ono Pharmaceutical Co., Ltd.

Merck Sharp & Dohme Corp.Ono Pharma USA, Inc.

最高研发阶段终止临床2/3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C11H22O2

InChIKeyYCYMCMYLORLIJX-SNVBAGLBSA-N

CAS号185517-21-9

关联

14

项与 Arundic acid 相关的临床试验

EUCTR2008-002079-28-HU / Not yet recruitingN/A

A Phase IIa Randomized, Double-Blind, Parallel-Groups, Placebo-Controlled ClinicalTrial to Study the Efficacy and Safety of MK-0724 Intravenous Infusion on theAmelioration of Neurological Damage and Recovery from Middle Cerebral ArteryIschemic Stroke

开始日期2008-10-30

申办/合作机构

Merck & Co., Inc.

NCT00694941 / Completed临床2期

A Phase II Multi-centre, Extension Study to Investigate the Long Term Safety of ONO-2506PO in Patients Diagnosed With Amyotrophic Lateral Sclerosis (ALS)

The objective of this study is to investigate the long term safety of ALS patients taking ONO-2506PO.

开始日期2008-06-01

申办/合作机构

Ono Pharmaceutical Co., Ltd.

EUCTR2007-004723-37-GB / Not yet recruitingN/A

A Phase II multi-centre, extension study to investigate the long term safety of ONO-2506PO in patients diagnosed with Amyotrophic Lateral Sclerosis (ALS).

开始日期2008-05-12

申办/合作机构

Ono Pharmaceutical Co., Ltd.

100 项与 Arundic acid 相关的临床结果

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100 项与 Arundic acid 相关的转化医学

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100 项与 Arundic acid 相关的专利（医药）

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47

项与 Arundic acid 相关的文献（医药）

2023-07-01·Neuroscience

ONO-2506 Can Delay Levodopa-induced Dyskinesia in the Early Stage

Article

作者: Cao, Xuebing ; Lian, Piaopiao ; Yuan, Yuhao ; Zhang, Xiaoqian ; Xu, Yan ; Wu, Yi

BACKGROUNDLevodopa-induced dyskinesia (LID) is a common motor complication of levodopa (L-DOPA) treatment for Parkinson's disease (PD). In recent years, the role of astrocytes in LID has increasingly attracted attention.OBJECTIVETo explore the effect of an astrocyte regulator (ONO-2506) on LID in a rat model and the potential underlying physiological mechanism.METHODSUnilateral LID rat models, established by administering 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle through stereotactic injection, were injected with ONO-2506 or saline into the striatum through brain catheterization and were administered L-DOPA to induce LID. Through a series of behavioral experiments, LID performance was observed. Relevant indicators were assessed through biochemical experiments.RESULTSIn the LID model of 6-OHDA rats, ONO-2506 significantly delayed the development and reduced the degree of abnormal involuntary movement in the early stage of L-DOPA treatment and increased glial fibrillary acidic protein and glutamate transporter 1 (GLT-1) expression in the striatum compared to saline. However, there was no significant difference in the improvement in motor function between the ONO-2506 and saline groups.CONCLUSIONSONO-2506 delays the emergence of L-DOPA-induced abnormal involuntary movements in the early stage of L-DOPA administration, without affecting the anti-PD effect of L-DOPA. The delaying effect of ONO-2506 on LID may be linked to the increased expression of GLT-1 in the rat striatum. Interventions targeting astrocytes and glutamate transporters are potential therapeutic strategies to delay the development of LID.

2023-05-01·Acta Neuropathologica

Spinal astrocyte dysfunction drives motor neuron loss in late-onset spinal muscular atrophy

Article

作者: Kleinschnitz, Christoph ; Hezel, Stefanie ; Steffen, Rebecca ; Leo, Markus ; Hagenacker, Tim ; Schara-Schmidt, Ulrike ; Roos, Andreas ; Schmitt, Linda-Isabell ; David, Christina

AbstractSpinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by a loss of the survival of motor neuron 1 (SMN1) gene, resulting in a loss of spinal motor neurons (MNs), leading to muscle weakness and wasting. The pathogenesis of MN loss in SMA and the selective vulnerability in different cellular populations are not fully understood. To investigate the role of spinal astrocytes in the pathogenesis of late-onset SMA, we used a mouse model in addition to in vitro approaches. Immunostaining, Western blot analysis, small interfering ribonucleic acid (siRNA) transfections, functional assays, enzyme-linked immunosorbent assay (ELISA), behavioral tests, and electrophysiological measurements were performed. Early activation of spinal astrocytes and a reduction of the excitatory amino acid transporter 1 (EAAT1) on postnatal day (P) 20 preceded the loss of spinal MNs in SMA mice occurring on P42. EAAT1 reduction resulted in elevated glutamate levels in the spinal cord of SMA mice at P20 and P42. SMA-like astrocytes generated by siRNA and an ex vivo model of glutamate excitotoxicity involving organotypic spinal cord slice cultures revealed the critical role of glutamate homeostasis in the degeneration of MNs. The pre-emptive administration of arundic acid (AA), as an inhibitor of astrocyte activation, to SMA mice prior to the loss of motor neurons (P28) resulted in elevated EAAT1 protein levels compared to vehicle-treated SMA mice and prevented the increase of glutamate in the spinal cord and the loss of spinal MNs. Furthermore, AA preserved motor functions during behavioral experiments, the electrophysiological properties, and muscle alteration of SMA mice. In a translational approach, we transfected healthy human fibroblasts with SMN1 siRNA, resulting in reduced EAAT1 expression and reduced uptake but increased glutamate release. These findings were verified by detecting elevated glutamate levels and reduced levels of EAAT1 in cerebrospinal fluid of untreated SMA type 2 and 3 patients. In addition, glutamate was elevated in serum samples, while EAAT1 was not detectable. Our data give evidence for the crucial role of spinal astrocytes in the pathogenesis of late-onset SMA, a potential driving force for MN loss by glutamate excitotoxicity caused by EAAT1 reduction as an early pathophysiological event. Furthermore, our study introduces EAAT1 as a potential therapeutic target for additional SMN-independent therapy strategies to complement SMN-enhancing drugs.

2023-04-01·Progress in Neuro-Psychopharmacology and Biological Psychiatry

Arundic acid (ONO-2506) downregulates neuroinflammation and astrocyte dysfunction after status epilepticus in young rats induced by Li-pilocarpine

Article

作者: Seady, Marina ; Leal, Miriara B ; Vizuete, Adriana Fernanda K ; Taday, Jéssica ; Moreira, Ana Paula ; Gonçalves, Carlos-Alberto

Astrocytes, the most abundant glial cells, have several metabolic functions, including ionic, neurotransmitter and energetic homeostasis for neuronal activity. Reactive astrocytes and their dysfunction have been associated with several brain disorders, including the epileptogenic process. Glial Fibrillary Acidic Protein (GFAP) and S100 calcium-binding protein B (S100B) are astrocyte biomarkers associated with brain injury. We hypothesize that arundic acid (ONO-2506), which is known as an inhibitor of S100B synthesis and secretion, protects the hippocampal tissue from neuroinflammation and astrocyte dysfunction after status epileptics (SE) induction by Li-pilocarpine in young rats. Herein, we investigated the effects of arundic acid treatment, at time points of 6 or 24 h after the induction of SE by Li-pilocarpine, in young rats. In SE animals, arundic acid was able to prevent the damage induced by Li-pilocarpine in the hippocampus, decreasing neuroinflammatory signaling (reducing IL-1β, COX2, TLR4 and RAGE contents), astrogliosis (decreasing GFAP and S100B) and astrocytic dysfunction (recovering levels of GSH, glutamine synthetase and connexin-43). Furthermore, arundic acid improved glucose metabolism and reduced the glutamate excitotoxicity found in epilepsy. Our data reinforce the role of astrocytes in epileptogenesis development and the neuroprotective role of arundic acid, which modulates astrocyte function and neuroinflammation in SE animals.

100 项与 Arundic acid 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06296	-	-	DB05343

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肌肉无力	临床3期	奥地利	Ono Pharmaceutical Co., Ltd.	2006-11-01
肌肉无力	临床3期	荷兰	Ono Pharmaceutical Co., Ltd.	2006-11-01
肌肉无力	临床3期	英国	Ono Pharmaceutical Co., Ltd.	2006-11-01
阿尔茨海默症	临床3期	美国	Ono Pharma USA, Inc.	2004-06-01
阿尔茨海默症	临床3期	加拿大	Ono Pharma USA, Inc.	2004-06-01
帕金森病	临床3期	-	Ono Pharmaceutical Co., Ltd.	2004-01-01
急性缺血性卒中	临床3期	加拿大	Ono Pharma USA, Inc.	2002-11-01
急性缺血性卒中	临床3期	美国	Ono Pharma USA, Inc.	2002-11-01
急性缺血性卒中	临床3期	加拿大	Ono Pharma USA, Inc.	2002-11-01
急性缺血性卒中	临床3期	美国	Ono Pharma USA, Inc.	2002-11-01