REN-1654(REN-1654) - 药物靶点：TNF-α x p38 MAPK_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [2]

靶点

TNF-α x p38 MAPK

作用机制

TNF-α抑制剂(肿瘤坏死因子α抑制剂)、p38 MAPK抑制剂(P38丝裂原活化蛋白激酶抑制剂)

治疗领域

免疫系统疾病感染神经系统疾病+ [4]

在研适应症-

非在研适应症

艾滋病痴呆复合征认知功能障碍运动失调+ [6]

原研机构

Evotec SE

在研机构-

非在研机构

Renovis, Inc.Centaur Pharmaceuticals, Inc.

Centaur Pharmaceuticals Pvt Ltd.

最高研发阶段终止临床2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C13H18N2O2

InChIKeyDJKNRCWSXSZACF-UHFFFAOYSA-N

CAS号183619-38-7

关联

4

项与 REN-1654 相关的临床试验

NCT00002414 / Unknown status临床2期

Randomized, Double-Blind, Parallel Group, Placebo Controlled, Tolerability, Safety and Pilot Efficacy Study of CPI-1189 in HIV Infected Individuals With Cognitive and Motor Impairment

The purpose of this study is to see if it is safe and effective to give CPI-1189 to patients with AIDS dementia.
Advanced HIV infection can cause AIDS dementia (brain damage due to HIV leading to loss of memory and muscle control). CPI-1189 may be able to postpone AIDS dementia or slow it down.

开始日期-

申办/合作机构

Centaur Pharmaceuticals, Inc.

NCT00107055 / Unknown status临床2期

REN-1654 in Sciatica: A Phase 2, Randomized, Double-Blind, Placebo Controlled, Multi-Center Study in Subjects With Pain Due to Lumbosacral Radiculopathy

The purpose of this study is to gain initial safety and efficacy data on the experimental agent REN-1654 in patients with pain that radiates down the leg(s), and is typical of sciatica (lumbosacral radiculopathy). These patients will usually have a herniated disc that is causing compression on the nerves coming out of the spinal column.

开始日期2003-12-01

申办/合作机构

Renovis, Inc.

NCT00099528 / Unknown status临床2期

REN-1654 in Post-Herpetic Neuralgia: a Multi-Center, Placebo Controlled, 3-week Dose-Finding Study, With a 3-Week Active-Treatment Extension

The purpose of this study is to gain initial safety and efficacy data on the experimental agent REN-1654 in patients with painful post-herpetic neuralgia (PHN).

开始日期2003-08-01

申办/合作机构

Renovis, Inc.

100 项与 REN-1654 相关的临床结果

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100 项与 REN-1654 相关的转化医学

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100 项与 REN-1654 相关的专利（医药）

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8

项与 REN-1654 相关的文献（医药）

2021-03-15·Aging3区 · 医学

CPI-1189 protects neuronal cells from oxygen glucose deprivation/re-oxygenation-induced oxidative injury and cell death

3区 · 医学

Article

作者: Li, Yong-Jun ; Zhan, Yueli ; Yang, Chengliang ; Li, Chengrui ; Sun, Jianhong

Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) induces profound oxidative injury and neuronal cell death. It mimics ischemia-reperfusion neuronal injury. CPI-1189 is a novel tumor necrosis factor alpha-inhibiting compound with potential neuroprotective function. Here in SH-SY5Y neuronal cells and primary murine cortical neurons, CPI-1189 pretreatment potently inhibited OGDR-induced viability reduction and cell death. In OGDR-stimulated neuronal cells, p38 phosphorylation was blocked by CPI-1189. In addition, CPI-1189 alleviated OGDR-induced reactive oxygen species production, lipid peroxidation, and glutathione consumption. OGDR-induced neuronal cell apoptosis was also inhibited by CPI-1189 pretreatment. Furthermore, in SH-SY5Y cells and cortical neurons, CPI-1189 alleviated OGDR-induced programmed necrosis by inhibiting mitochondrial p53-cyclophilin D-adenine nucleotide translocase 1 association, mitochondrial depolarization, and lactate dehydrogenase release to the medium. In summary, CPI-1189 potently inhibited OGDR-induced oxidative injury and neuronal cell death.

2014-01-14·Pain Physician3区 · 医学

Anti-Tumor Necrosis Factor Antagonists in the Treatment of Low Back Pain and Radiculopathy: A Systematic Review and Meta-analysis

3区 · 医学

Review

作者: Ramsin M Benyamin ; Janini Chen ; Daniel C Pimentel ; Omar El Abd ; Anna M Buehler ; Joao E D Amadera ; Wu Tu Hsing ; Danesh Mazloomdoost ; Victor F Leite

Background: Low back pain, with or without radiculopathy, is an important cause of disability and economic expenditure. However, many patients are not achieving optimal pain control with existing medications. Tumor necrosis factor antagonists (anti-TNFα) could be an alternative drug treatment. Objectives: Systematic review the efficacy and safety of anti-TNFα in the treatment of low back pain with or without radiculopathy. Study Design: Inclusion criteria were observational studies with safety as an outcome, and randomized or nonrandomized controlled trial (RCT) studies on efficacy and/or safety of antiTNFα drugs on low back pain. Exclusion criteria included patients with auto-immune conditions or osteoporosis. Results: Studies were assessed independently by 2 authors regarding inclusion/exclusion criteria, risk of bias, clinical relevance, quality, and strength of evidence (GRADE approach). Of the 1,179 studies retreived,all duplicates were excluded and then the inclusion/exclusion criteria was applied. One observational study (n = 143) and 11 RCTs remained (n = 539): 8 for etanercept (n = 304), one for adalimumab (n = 61), one for adalimumab and etanercept (n = 60), one for infliximab (n = 40) and one for REN-1654 (n = 74). Only 3 etanercept and 2 adalimumab studies showed statistically significant pain relief when compared to placebo. There was no difference in the overall incidence of adverse effects when comparing anti-TNF-α and placebo. Limitations: Despite the statistically significant effect, this meta-analysis has important limitations, such as high heterogeneity and high use of outcome imputation. Conclusions: There is low evidence that epidural etanercept has a low-to-moderate effect size when compared to placebo for pain due to discogenic lumbar radiculopathy (5 studies, n=185), with a standardized mean difference = -0.43 (95% confidence interval [CI] -0.84 to -0.02). There is moderate evidence that epidural etanercept does not have a higher adverse effects incidence rate when compared to placebo for discogenic lumbar radiculopathy (5 studies, n = 185) with a relative risk (RR) = 0.84 (95% CI 0.53 to 1.34). There is moderate evidence that anti-TNFα does not have a higher adverse effects incidence rate when compared to placebo for low back pain (10 studies, n= 343) with an RR = 0.93 (95% CI 0.56 to 1.55). We strongly suggest that anti-TNFα continue to be studied in experimental settings for the treatment of low back pain. We cannot currently recommend this therapy in clinical practice. New research could shed some light on the efficacy of anti-TNFα and change this recommendation in the future. Key words: Low back pain, systematic review, meta-analysis, tumor necrosis factor-alpha, TNF, biologics, tumor necrosis factor-alpha antagonists, anti-TNF, etanercept, adalimumab, discogenic lumbar radiculopathy, sciatica.

2002-12-01·Current opinion in investigational drugs (London, England : 2000)

CPI-1189. Centaur.

Review

作者: Müller, Thomas

The efficacy of the proapoptotic cytokine tumor necrosis factor (TNF) alpha-inhibiting compound CPI-1189 has been demonstrated in various cell culture and animal models of chronic neurodegenerative and inflammatory diseases. CPI-1189 intracellularly inhibits the p38 mitogen-activated protein kinase phosphoactivation, thereby protecting against TNF alpha-induced neurodegeneration. Clinical proof-of-concept phase IIa trials in patients with Parkinson's disease and AIDS dementia complex were successful. These studies demonstrated clinical relevance for treatment with CPI-1189 (50 to 100 mg/day), which attenuated the deterioration in cognitive and/or motor function without any relevant side effects. Since the importance of neuroprotection is emerging, in particular in neurodegenerative diseases with concomitant observed immunological pro-apoptotic alterations in the central nervous system, long-term application of CPI-1189 could represent a promising future therapeutic alternative, in addition to neuroprotective compounds such as selegiline.

100 项与 REN-1654 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12311

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
椎间盘疾病	临床2期	美国	Renovis, Inc.	2003-12-01
腰骶神经根病变	临床2期	美国	Renovis, Inc.	2003-12-01
坐骨神经痛	临床2期	美国	Renovis, Inc.	2003-12-01
带状疱疹	临床2期	美国	Renovis, Inc.	2003-08-01
疱疹后神经痛	临床2期	美国	Renovis, Inc.	2003-08-01
艾滋病痴呆复合征	临床2期	美国	Centaur Pharmaceuticals, Inc.	2001-08-31
艾滋病痴呆复合征	临床2期	美国	Centaur Pharmaceuticals, Inc.	2001-08-31
认知功能障碍	临床2期	美国	Centaur Pharmaceuticals, Inc.	2001-08-31
运动失调	临床2期	美国	Centaur Pharmaceuticals, Inc.	2001-08-31
炎症性肠病	临床2期	美国	Renovis, Inc.	-