Ornithine Phenylacetate(Ornithine Phenylacetate) - 药物靶点：NF-κB x NOS2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

L-Ornithine phenylacetate、Ornithine hydrochloride/sodium phenylacetate、Ornithine phenylacetate (USAN)

+ [8]

靶点

NF-κB x NOS2

作用机制

NF-κB抑制剂(核因子NF-κB复合体抑制剂)、NOS2调节剂(诱导型一氧化氮合酶调节剂)

治疗领域

神经系统疾病消化系统疾病内分泌与代谢疾病+ [1]

在研适应症-

非在研适应症

药物性肝损伤纤维化肝性脑病+ [3]

原研机构

University College London

在研机构-

非在研机构

OCERA Therapeutics LLC

Mallinckrodt Plc

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (欧盟)

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结构/序列

分子式C13H20N2O4

InChIKeyLRSYFEZBIMVWRY-VWMHFEHESA-N

CAS号952154-79-9

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关联

9

项与 Ornithine Phenylacetate 相关的临床试验

NCT04128462

/ Withdrawn临床3期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of MNK6105 (an Intravenous Formulation of L-Ornithine Phenylacetate) in Hospitalized Patients With Cirrhosis and Hyperammonemia Associated With an Episode of Hepatic Encephalopathy

This study is for patients with cirrhosis and hepatic encephalopathy who are in the hospital. This means they have a high ammonia level which is affecting their brain function.
All patients will receive the standard of (regular) care. Each will have an equal chance (like flipping a coin) of receiving the experimental drug or placebo along with the standard care.
Each patient will have tests during the first 24 hours, receive treatment for up to 5 days, and have 30 days of follow-up.

开始日期2021-11-01

申办/合作机构

Mallinckrodt Plc

NCT03712280

/ Completed临床2期

A Randomized, Open-Label, Phase 2a Comparator Study to Assess the Pharmacodynamics, Safety and Pharmacokinetics of Oral Administration MNK6106 (L-Ornithine Phenylacetate) Versus Rifaximin in Subjects With Hepatic Cirrhosis and a History of Prior Episodes of Hepatic Encephalopathy

The main reason for this study is to see how the study drug interacts with the body.
It will compare different doses of the study drug with a drug already in use.
Participants will be adults with liver disease that has affected the brain in the past.

开始日期2018-12-01

申办/合作机构

Mallinckrodt Plc

NCT03846843

/ Completed临床1期

An Open-Label, Two-Part, Phase 1/2a, Crossover Study to Determine the Absolute Bioavailability and Pharmacokinetics of Oral Immediate-Release Doses of OCR-002 in Subjects With Varying Degrees of Cirrhosis

This is an open-label Phase 1, 2-part, crossover study in approximately 33 adult subjects (12 subjects in Part 1 and 21 subjects in Part 2), with varying degrees of cirrhosis with analysis of pharmacokinetic (PK) data after Part 1 to guide dose regimen selection and PK sampling time points for OCR-002 in Part 2.

开始日期2016-08-15

申办/合作机构

OCERA Therapeutics LLC

100 项与 Ornithine Phenylacetate 相关的临床结果

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100 项与 Ornithine Phenylacetate 相关的转化医学

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100 项与 Ornithine Phenylacetate 相关的专利（医药）

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1,555

项与 Ornithine Phenylacetate 相关的文献（医药）

2025-02-01·Free Radical Biology and Medicine

Spinal AT1R contributes to neuroinflammation and neuropathic pain via NOX2-dependent redox signaling in microglia

Article

作者: Liu, Baowen ; Zhang, Wencui ; Jiao, Bo ; Sun, Jiaoli ; Zhang, Xianwei ; Zhang, Kaiwen ; Yu, Shangchen

Microglia-mediated neuroinflammation demonstrates a crucial act in the progression of neuropathic pain. Oxidative damage induced by reactive oxygen species (ROS) derived from NADPH oxidase (NOX) in microglia drives proinflammatory microglia activation. Recent evidence points to the central renin angiotensin system (RAS) is involved in oxidative stress and neuroinflammation, with the angiotensin converting enzyme/angiotensin II/angiotensin receptor-1 (ACE/Ang II/AT1R) axis promoting inflammation through increased ROS production, counteracted by the ACE2/Ang (1-7)/Mas receptor (MasR) axis. While interventions targeting spinal AT1R have been shown to alleviate nociceptive hypersensitivity; yet the mechanisms remain elusive. Here, we discovered that spared nerve injury (SNI)-induced mechanical allodynia in rats were associated with M1-like microglia activation, oxidative stress and overactivity of ACE/Ang II/AT1R axis in the spinal cord. Increased AT1R and NOX2 expression were observed in activated dorsal horn microglia following SNI. Blockade of AT1R with losartan potassium (LOP) suppressed NOX2-mediated oxidative stress, and promoted a shift in microglia from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype in LPS-treated BV-2 cells. Additionally, NOX2 overexpression triggered the activation of the high-mobility group box 1/nuclear factor-kappa B (HMGB1/NF-κB) signaling pathway. Intrathecal administration of LOP effectively inhibited SNI-induced NOX2 overactivation in microglia and suppressed the HMGB1/NF-kB pathway, reducing oxidative stress and shifting the microglia polarization from M1 to M2 in the spinal cord, thereby attenuating neuroinflammation and pain hypersensitivity. Collectively, these findings underscore the neuroimmune-modulating effects of spinal AT1R in neuropathic pain, highlighting the regulation of redox homeostasis in microglia via a NOX2 dependent mechanism.

2025-02-01·Current Computer-Aided Drug Design

Exploring the Mechanisms of Sanguinarine in the Treatment of Osteoporosis by Integrating Network Pharmacology Analysis and Deep Learning Technology

Article

作者: Zhou, Daoqing ; Yao, Zhicheng ; Tang, Yonghong ; Zeng, Yuqing ; Gan, Fengping

Background:Sanguinarine (SAN) has been reported to have antioxidant, antiinflammatory, and antimicrobial activities with potential for the treatment of osteoporosis (OP).Objective:This work purposed to unravel the molecular mechanisms of SAN in the treatment of OP.Methods:OP-related genes and SAN-related targets were predicted from public databases. Differential expression analysis and VennDiagram were adopted to detect SAN-related targets against OP. Protein-protein interaction (PPI) network was served for core target identification. Molecular docking and DeepPurpose algorithm were further adopted to investigate the binding ability between core targets and SAN. Gene pathway scoring of these targets was calculated utilizing gene set variation analysis (GSVA). Finally, we explored the effect of SAN on the expressions of core targets in preosteoblastic MC3T3-E1 cells.Results:A total of 21 candidate targets of SAN against OP were acquired. Furthermore, six core targets were identified, among which CASP3, CTNNB1, and ERBB2 were remarkably differentially expressed in OP and healthy individuals. The binding energies of SAN with CASP3, CTNNB1, and ERBB2 were -6, -6.731, and -7.162 kcal/mol, respectively. Moreover, the GSVA scores of the Wnt/calcium signaling pathway were significantly lower in OP cases than in healthy individuals. In addition, the expression of CASP3 was positively associated with Wnt/calcium signaling pathway. CASP3 and ERBB2 were significantly lower expressed in SAN group than in DMSO group, whereas the expression of CTNNB1 was in contrast.Conclusion:CASP3, CTNNB1, and ERBB2 emerge as potential targets of SAN in OP prevention and treatment.

2025-01-15·The Journal of Maternal-Fetal & Neonatal Medicine4区 · 医学

Organophosphate pesticide exposure prenatally influence on pregnancy outcomes

4区 · 医学

Article

作者: Mukattash, Tareq L. ; Tahaineh, Linda ; Al-Mehaisen, Lama M. ; Al-Kuran, Oqba ; Nuseir, Khawla Q. ; Ayoub, Nehad M. ; Al-Rawi, Naseer

BACKGROUNDOrganophosphorus (OP) pesticides are widely used worldwide. The effect of OP exposure during pregnancy on the offspring is inconsistent in the current literature. Moreover, similar studies in the Middle East are lacking.PURPOSETo examine the effects of OP exposure in utero on the outcome of pregnancies in an agricultural region in Jordan.METHODA prospective study, employing a questionnaire to collect women demographic data. Hospital records were collected for newborns' birth data. In addition, urine samples during the third trimester were collected from pregnant women and then analyzed for six OP metabolites to measure exposure.RESULTSOne of the metabolites, DEDTP, was negatively correlated with gestational age and Apgar scores 1 and 5. There were no other significant associations.CONCLUSIONSExposure to OP during pregnancy is not highly associated with any negative anthropometric characteristics of the newborns; it is probably offset by other factors.

100 项与 Ornithine Phenylacetate 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09942	-	-	-

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
纤维化	临床3期	-	Mallinckrodt Plc	2021-11-01
纤维化	临床3期	-	Mallinckrodt Plc	2021-11-01
肝性脑病	临床3期	-	Mallinckrodt Plc	2021-11-01
肝性脑病	临床3期	-	Mallinckrodt Plc	2021-11-01
高氨血症	临床3期	-	Mallinckrodt Plc	2021-11-01
高氨血症	临床3期	-	Mallinckrodt Plc	2021-11-01
肝硬化	临床3期	波多黎各	Mallinckrodt Plc	2018-12-01
肝硬化	临床3期	美国	Mallinckrodt Plc	2018-12-01
药物性肝损伤	临床3期	美国	OCERA Therapeutics LLC	2012-06-01
急性肝功能衰竭	临床3期	美国	OCERA Therapeutics LLC	2012-06-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01966419 (STOP-HE, Pubmed \| Clin Gastroenterol Hepatol) 人工标引	临床2期	肝性脑病	226	Ornithine Phenylacetate	(糧襯艱壓顧顧餘鹽製糧) = 構鹽構製構窪顧廠觸鏇壓網憲糧壓衊壓願積淵 (簾齋遞獵壓襯醖選鹹鑰, 34 ~ 69) 更多	不佳	2021-12-01
				Placebo	(糧襯艱壓顧顧餘鹽製糧) = 醖鬱鹹簾顧遞蓋衊顧醖壓網憲糧壓衊壓願積淵 (簾齋遞獵壓襯醖選鹹鑰, 53 ~ 98) 更多
NCT01966419 (STOP-HE, CTgov)	临床2期	肝性脑病 \| 纤维化 \| 高氨血症	231	placebo intravenous infusion (Placebo)	壓製獵選襯醖蓋夢製顧(糧糧願廠願醖願觸範淵) = 鹹範積鹹夢繭鏇鬱艱構夢淵鬱簾繭襯範築襯衊 (鑰網遞構構簾選糧製積, 選鏇襯蓋範積憲網製製 ~ 顧襯選簾壓蓋憲獵艱壓) 更多	-	2021-09-16
				ornithine phenylacetate (Ornithine Phenylacetate)	壓製獵選襯醖蓋夢製顧(糧糧願廠願醖願觸範淵) = 糧窪襯醖醖糧鹽廠簾鏇夢淵鬱簾繭襯範築襯衊 (鑰網遞構構簾選糧製積, 廠鬱製繭範繭衊遞繭憲 ~ 顧顧糧鹹構壓繭簾餘襯) 更多
NCT03712280 (CTgov)	临床2期	肝性脑病 \| 肝硬化	50	MNK6106 (Group A: MNK6106 2 Grams (Tid))	獵網網蓋糧選膚壓獵鹽(襯積鹹鹹壓選網衊齋鬱) = 憲膚網繭壓觸繭遞齋衊壓鑰窪齋艱蓋夢觸膚鬱 (膚鏇齋繭淵鹹鏇鏇夢窪, 顧餘壓鏇顧膚繭醖鹹範 ~ 鑰鬱積築齋網膚遞壓鬱) 更多	-	2021-07-20
				MNK6106 (Group B: MNK6106 4 Grams (Bid))	獵網網蓋糧選膚壓獵鹽(襯積鹹鹹壓選網衊齋鬱) = 艱鹹觸鏇壓鹹範積艱窪壓鑰窪齋艱蓋夢觸膚鬱 (膚鏇齋繭淵鹹鏇鏇夢窪, 築獵齋範糧鹽遞壓窪選 ~ 襯鑰夢顧網窪廠簾蓋鏇) 更多