Delving into the Latest Updates on Arbaclofen Placarbil with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Arbaclofen placarbil (USAN/INN), XP-19986, XP19986

Target

GABAB receptor

Action

agonists

Mechanism

GABAB receptor agonists(Gamma-Aminobutyric Acid B Receptor agonists)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesSkin and Musculoskeletal Diseases+ [4]

Active Indication-

Inactive Indication

Acute low back painAlcohol Use DisorderGastroesophageal Reflux+ [4]

Originator Organization

XenoPort, Inc.

Active Organization-

Inactive Organization

XenoPort, Inc.Indivior, Inc.

License Organization

Reckitt Benckiser Group Plc

XenoPort, Inc.

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC19H26ClNO6

InChIKeyJXTAALBWJQJLGN-KSSFIOAISA-N

CAS Registry847353-30-4

Part 1
* To evaluate the pharmacokinetic (PK) profile of Arbaclofen Placarbil (AP) and R-baclofen following dosing of Arbaclofen Placarbil Modified Release (MR) Prototype A Tablet and Arbaclofen Placarbil MR Prototype B Tablet in healthy subjects
* To determine the relative bioavailability of AP and R-baclofen following dosing of Arbaclofen Placarbil MR Prototype A Tablet and Arbaclofen Placarbil MR Prototype B Tablet compared to the reference Arbaclofen Placarbil Sustained Release (SR) Tablets (low dose)
* To determine the relative bioavailability and PK of AP and R-baclofen following dosing of the selected MR prototype formulation(s) in the presence of beverage
* To provide additional information on the safety and tolerability of single doses of AP
Part 2
* To evaluate the PK profile of AP and R-baclofen following dosing of Arbaclofen Placarbil MR Prototype Tablets in healthy subjects
* To determine the relative bioavailability and PK of AP and R-baclofen following dosing of Arbaclofen Placarbil MR Prototype Tablets compared to the reference Arbaclofen Placarbil Immediate Release (IR) Capsule
* To provide additional information on the safety and tolerability of single doses of AP
* To determine the relative bioavailability and PK of AP and R-baclofen following dosing of a selected MR prototype formulation in the fed state (optional)
* To explore a possible in vitro in vivo correlation/relationship (IVIVC/IVIVR) for the Arbaclofen Placarbil MR Prototype Tablet Formulations
Part 3
* To determine the relative bioavailability of the selected Arbaclofen Placarbil MR Prototype Tablet in the presence of either beverage or food and/or
* To evaluate the PK profile (dose proportionality) of AP and R-baclofen following dosing of the selected Arbaclofen Placarbil MR Prototype A + B Tablet at different dose levels in healthy subjects
* To provide additional information on the safety and tolerability of single doses of AP

Start Date24 Jan 2017

Sponsor / Collaborator

Indivior, Inc.

NCT02511886

/ CompletedPhase 2

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Determine the Maximum Tolerated Dose of Arbaclofen Placarbil in Subjects With Alcohol Use Disorder

This study will determine the maximum tolerated dose (MTD) of arbaclofen placarbil (AP) in the treatment of subjects with Alcohol Use Disorder (AUD). For every two subjects receiving AP, one subject will receive placebo.

Start Date01 Sep 2015

Sponsor / Collaborator

Indivior, Inc.

NCT01359566

/ CompletedPhase 3

A Randomized, Double Blind, Placebo-Controlled Efficacy and Safety Study of Arbaclofen Placarbil in Subjects With Spasticity Due to Multiple Sclerosis

To evaluate the efficacy of three doses of XP19986 (arbaclofen placarbil) compared to placebo for the treatment of spasticity in subjects with multiple sclerosis (MS).

Start Date01 May 2011

Sponsor / Collaborator

XenoPort, Inc.

100 Clinical Results associated with Arbaclofen Placarbil

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100 Translational Medicine associated with Arbaclofen Placarbil

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100 Patents (Medical) associated with Arbaclofen Placarbil

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14

Literatures (Medical) associated with Arbaclofen Placarbil

30 Jul 2024·JOURNAL OF ALZHEIMERS DISEASE

Screening Targets and Therapeutic Drugs for Alzheimer’s Disease Based on Deep Learning Model and Molecular Docking

Article

Author: Zhao, Pu ; Li, Jia-Yi ; Zhong, Man-Li ; Gao, Hui-Ling ; Zhang, Ya-Hong

Background::

Alzheimer’s disease (AD) is a neurodegenerative disorder caused by a complex interplay of various factors. However, a satisfactory cure for AD remains elusive. Pharmacological interventions based on drug targets are considered the most cost-effective therapeutic strategy. Therefore, it is paramount to search potential drug targets and drugs for AD.

Objective::

We aimed to provide novel targets and drugs for the treatment of AD employing transcriptomic data of AD and normal control brain tissues from a new perspective.

Methods::

Our study combined the use of a multi-layer perceptron (MLP) with differential expression analysis, variance assessment and molecular docking to screen targets and drugs for AD.

Results::

We identified the seven differentially expressed genes (DEGs) with the most significant variation (ANKRD39, CPLX1, FABP3, GABBR2, GNG3, PPM1E, and WDR49) in transcriptomic data from AD brain. A newly built MLP was used to confirm the association between the seven DEGs and AD, establishing these DEGs as potential drug targets. Drug databases and molecular docking results indicated that arbaclofen, baclofen, clozapine, arbaclofen placarbil, BML-259, BRD-K72883421, and YC-1 had high affinity for GABBR2, and FABP3 bound with oleic, palmitic, and stearic acids. Arbaclofen and YC-1 activated GABA B receptor through PI3K/AKT and PKA/CREB pathways, respectively, thereby promoting neuronal anti-apoptotic effect and inhibiting p-tau and Aβ formation.

Conclusions::

This study provided a new strategy for the identification of targets and drugs for the treatment of AD using deep learning. Seven therapeutic targets and ten drugs were selected by using this method, providing new insight for AD treatment.

15 Jan 2021·ORGANIC PROCESS RESEARCH & DEVELOPMENT

Process Development toward a Pro-Drug of R-Baclofen

Author: Allsop, Glyn L. ; Carey, John S. ; Joshi, Sudhir ; Mirata, Marco A. ; Leong, Paul

This paper describes the process development conducted toward the multi-kilogram synthesis of a novel transported pro-drug of R-baclofen.The key steps in the synthesis were the enzyme-catalyzed kinetic resolution of isopropyl(methylthiocarbonyloxy)methyl-2-methylpropionate using Candida antarctica lipase A to provide the desired (S)-enantiomer.This was followed by the reaction with sulfuryl chloride and N-hydroxysuccinimide to produce (S) 1-(2,5-dioxoazolidinyloxycarbonyloxy)-2-methylpropyl 2-methylpropanate.The synthesis of (S) 1-(2,5-dioxoazolidinyloxycarbonyloxy)-2-methylpropyl 2-methylpropanate enabled the efficient use of R-baclofen in the final coupling stage of the synthesis.The new route reported here is more efficient and sustainable than those reported previously and had the potential to become the com. route of manufacture

01 Dec 2020·European journal of medicinal chemistryQ1 · MEDICINE

(Carbonyl)oxyalkyl linker-based amino acid prodrugs of the HIV-1 protease inhibitor atazanavir that enhance oral bioavailability and plasma trough concentration

Q1 · MEDICINE

Article

Author: Ramar, Thangeswaran ; Arla, Rambabu ; Jenkins, Susan M ; Padmanabhan, Shweta ; Meanwell, Nicholas A ; Desai, Salil D ; Krystal, Mark R ; Sinha, Sarmistha ; Bhutani, Priyadeep ; Subbaiah, Murugaiah A M ; Subramani, Lakshumanan ; Subramanian, Murali ; Mandlekar, Sandhya ; Kadow, John F ; Sridhar, Srikanth

We describe the design, synthesis and pharmacokinetic (PK) evaluation of a series of amino acid-based prodrugs of the HIV-1 protease inhibitor atazanavir (1) derivatized on the pharmacophoric secondary alcohol using a (carbonyl)oxyalkyl linker. Prodrugs of 1 incorporating simple (carbonyl)oxyalkyl-based linkers and a primary amine in the promoiety were found to exhibit low chemical stability. However, chemical stability was improved by modifying the primary amine moiety to a tertiary amine, resulting in a 2-fold enhancement of exposure in rats following oral dosing compared to dosing of the parent drug 1. Further refinement of the linker resulted in the discovery of 22 as a prodrug that delivered the parent 1 to rat plasma with a 5-fold higher AUC and 67-fold higher C₂₄ when compared to oral administration of the parent drug. The PK profile of 22 indicated that plasma levels of this prodrug were higher than that of the parent, providing a more sustained release of 1 in vivo.

100 Deals associated with Arbaclofen Placarbil

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External Link

KEGG	Wiki	ATC	Drug Bank
D08861	Arbaclofen Placarbil	-	DB08892

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis, Relapsing-Remitting	Phase 3	United States	XenoPort, Inc.	01 May 2011
Multiple Sclerosis, Secondary Progressive	Phase 3	United States	XenoPort, Inc.	01 May 2011
Muscle Spasticity	Phase 3	United States	XenoPort, Inc.	01 May 2011
Alcohol Use Disorder	Phase 2	United States	Indivior, Inc.	01 Sep 2015
Acute low back pain	Phase 2	United States	XenoPort, Inc.	01 Dec 2008
Spinal Cord Injuries	Phase 2	United States	XenoPort, Inc.	01 Dec 2007
Gastroesophageal Reflux	Phase 2	United States	Indivior, Inc.	01 Oct 2005