Delving into the Latest Updates on Ornithine Phenylacetate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

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

+ [8]

Target

NF-κB x NOS2

Mechanism

NF-κB inhibitors(Nuclear factor NF-kappa-B complex inhibitors), NOS2 modulators(Nitric oxide synthase, inducible modulators)

Therapeutic Areas

Nervous System DiseasesDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Chemical and Drug Induced Liver InjuryFibrosisHepatic Encephalopathy+ [3]

Originator Organization

University College London

Active Organization-

Inactive Organization

OCERA Therapeutics LLC

Mallinckrodt Plc

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (EU)

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Structure/Sequence

Molecular FormulaC13H20N2O4

InChIKeyLRSYFEZBIMVWRY-VWMHFEHESA-N

CAS Registry952154-79-9

View All Structures (2)

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.

Start Date01 Nov 2021

Sponsor / Collaborator

Mallinckrodt Plc

NCT03712280

/ CompletedPhase 2

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.

Start Date01 Dec 2018

Sponsor / Collaborator

Mallinckrodt Plc

NCT03846843

/ CompletedPhase 1

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.

Start Date15 Aug 2016

Sponsor / Collaborator

OCERA Therapeutics LLC

100 Clinical Results associated with Ornithine Phenylacetate

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100 Translational Medicine associated with Ornithine Phenylacetate

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100 Patents (Medical) associated with Ornithine Phenylacetate

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1,555

Literatures (Medical) associated with Ornithine Phenylacetate

01 Feb 2025·Free Radical Biology and Medicine

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

Article

Author: 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.

01 Feb 2025·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

Author: 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.

15 Jan 2025·The Journal of Maternal-Fetal & Neonatal MedicineQ4 · MEDICINE

Organophosphate pesticide exposure prenatally influence on pregnancy outcomes

Q4 · MEDICINE

Article

Author: 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 Deals associated with Ornithine Phenylacetate

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External Link

KEGG	Wiki	ATC	Drug Bank
D09942	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fibrosis	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Fibrosis	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Hepatic Encephalopathy	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Hepatic Encephalopathy	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Hyperammonemia	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Hyperammonemia	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Liver Cirrhosis	Phase 3	PR	Mallinckrodt Plc	01 Dec 2018
Liver Cirrhosis	Phase 3	US	Mallinckrodt Plc	01 Dec 2018
Chemical and Drug Induced Liver Injury	Phase 3	US	OCERA Therapeutics LLC	01 Jun 2012
Liver Failure, Acute	Phase 3	US	OCERA Therapeutics LLC	01 Jun 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01966419 (STOP-HE, Pubmed \| Clin Gastroenterol Hepatol) Manual	Phase 2	Hepatic Encephalopathy	226	Ornithine Phenylacetate	(pwbbmqgeyj) = dfmmkwopzx mjfnbfgyls (alewlfgbuj, 34 - 69) View more	Negative	01 Dec 2021
				Placebo	(pwbbmqgeyj) = tooppbvmzi mjfnbfgyls (alewlfgbuj, 53 - 98) View more
NCT01966419 (STOP-HE, CTgov)	Phase 2	Hepatic Encephalopathy \| Fibrosis \| Hyperammonemia	231	placebo intravenous infusion (Placebo)	urjtqajmqq(plprcsdhut) = vjpewfpyqc rqsxieathr (jerpyzoidu, shmrkhuevn - cosonmydgo) View more	-	16 Sep 2021
				ornithine phenylacetate (Ornithine Phenylacetate)	urjtqajmqq(plprcsdhut) = vuzsvlumyi rqsxieathr (jerpyzoidu, rtdaevghmk - pafpzyqmij) View more
NCT03712280 (CTgov)	Phase 2	Hepatic Encephalopathy \| Liver Cirrhosis	50	MNK6106 (Group A: MNK6106 2 Grams (Tid))	cvkakgvqxo(aqqjghjqsn) = pbuuzgrssq ubzxlqifnv (iizujgbisk, wyjkegszjc - vnqtzygzvv) View more	-	20 Jul 2021
				MNK6106 (Group B: MNK6106 4 Grams (Bid))	cvkakgvqxo(aqqjghjqsn) = pionnxdnzn ubzxlqifnv (iizujgbisk, vfkqpksztv - cggwwdnoem) View more