BCI-838(BCI-838) - 药物靶点：mGluR2 x mGluR3_在研适应症：阿尔茨海默症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

mGluR2 x mGluR3

作用机制

mGluR2激动剂(代谢型谷氨酸受体2激动剂)、mGluR3激动剂(代谢型谷氨酸受体-3激动剂)

治疗领域

神经系统疾病

在研适应症

阿尔茨海默症

非在研适应症

重度抑郁症

原研机构

Taisho Pharmaceutical Co., Ltd.

在研机构

BrainCells, Inc.

非在研机构

Taisho Pharmaceutical Holdings Co., Ltd.

最高研发阶段临床前

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C22H28Cl2FNO5

InChIKeySVZJNGHWEHDHLT-OUSKECTQSA-N

CAS号820244-38-0

关联

3

项与 BCI-838 相关的临床试验

NCT01548703 / Completed临床1期

A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of BCI 838 in Healthy Adult Subjects

This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of BCI-838 and its metabolite BCI-632 in healthy male and female subjects.

开始日期2012-02-01

申办/合作机构

BrainCells, Inc.

NL-OMON37895 / CompletedN/A

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, ASCENDING MULTIPLE DOSE, SAFETY, TOLERABILITY PHARMACODYNAMIC AND PHARMACOKINETIC STUDY OF BCI 838 IN HEALTHY ADULT SUBJECTS - BCI-838 MAD study, tolerabilty, uptake and distribution study

开始日期2012-02-01

申办/合作机构

BrainCells, Inc.

NCT01546051 / Completed临床1期

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetic and Food Effect of BCI-838; and, An Open-Label Minidose Bioavailability Study to Compare Several BCI-632 Pro-drug Candidates in Healthy Male Subjects

This study will evaluate the safety, tolerability and pharmacokinetics of BCI-838, its metabolite BCI-632 and several new pro-drugs in healthy male subjects.

开始日期2011-10-01

申办/合作机构

BrainCells, Inc.

100 项与 BCI-838 相关的临床结果

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100 项与 BCI-838 相关的转化医学

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100 项与 BCI-838 相关的专利（医药）

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5

项与 BCI-838 相关的文献（医药）

2023-02-01·Neuroscience Letters

BCI-838, an orally active mGluR2/3 receptor antagonist pro-drug, rescues learning behavior deficits in the PS19 MAPT mouse model of tauopathy

Article

作者: Perez, Gissel M ; Barlow, Carrolee ; Sano, Mary ; Elder, Gregory A ; Gage, Fred H ; De Gasperi, Rita ; Bicak, Mesude ; Ehrlich, Michelle E ; Perez-Garcia, Georgina ; Otero-Pagan, Alena ; Haure-Mirande, Jean-Vianney ; Readhead, Benjamin ; Gama Sosa, Miguel A ; Gandy, Sam

Tauopathies are a heterogeneous group of neurodegenerative disorders that are clinically and pathologically distinct from Alzheimer's disease (AD) having tau inclusions in neurons and/or glia as their most prominent neuropathological feature. BCI-838 (MGS00210) is a group II metabotropic glutamate receptor (mGluR2/3) antagonist pro-drug. Previously, we reported that orally administered BCI-838 improved learning behavior and reduced anxiety in Dutch (APP^E693Q) transgenic mice, a model of the pathological accumulation of Aβ oligomers found in AD. Herein, we investigated effects of BCI-838 on PS19 male mice that express the tauopathy mutation MAPT^P301S associated with human frontotemporal lobar degeneration (FTLD). These mice develop an aging-related tauopathy without amyloid accumulation. Mice were divided into three experimental groups: (1) non-transgenic wild type mice treated with vehicle, (2) PS19 mice treated with vehicle and (3) PS19 mice treated with 5 mg/kg BCI-838. Groups of 10-13 mice were utilized. Vehicle or BCI-838 was administered by oral gavage for 4 weeks. Behavioral testing consisting of a novel object recognition task was conducted after drug administration. Two studies were performed beginning treatment of mice at 3 or 7 months of age. One month of BCI-838 treatment rescued deficits in recognition memory in PS19 mice whether treatment was begun at 3 or 7 months of age. These studies extend the potential utility of BCI-838 to neurodegenerative conditions that have tauopathy as their underlying basis. They also suggest an mGluR2/3 dependent mechanism as a basis for the behavioral deficits in PS19 mice.

2019-02-01·Neuropharmacology2区 · 医学

Blast-induced "PTSD": Evidence from an animal model

2区 · 医学

Review

作者: Tschiffely, Anna E ; Perez-Garcia, Georgina ; Ahlers, Stephen T ; McCarron, Richard M ; Hof, Patrick R ; Gandy, Sam ; Gama Sosa, Miguel A ; Elder, Gregory A ; De Gasperi, Rita

A striking observation among veterans returning from the recent conflicts in Iraq and Afghanistan has been the co-occurrence of blast-related mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI might coexist due to additive effects of independent psychological and physical traumas experienced in a war zone. Alternatively blast injury might induce PTSD-related traits or damage brain structures that mediate responses to psychological stressors, increasing the likelihood that PTSD will develop following a subsequent psychological stressor. Rats exposed to repetitive low-level blasts consisting of three 74.5 kPa exposures delivered once daily for three consecutive days develop a variety of anxiety and PTSD-related behavioral traits that are present for at least 9 months after blast exposure. A single predator scent challenge delivered 8 months after the last blast exposure induces additional anxiety-related changes that are still present 45 days later. Because the blast injuries occur under general anesthesia, it appears that blast exposure in the absence of a psychological stressor can induce chronic PTSD-related traits. The reaction to a predator scent challenge delivered many months after blast exposure suggests that blast exposure in addition sensitizes the brain to react abnormally to subsequent psychological stressors. The development of PTSD-related behavioral traits in the absence of a psychological stressor suggests the existence of blast-induced "PTSD". Findings that PTSD-related behavioral traits can be reversed by BCI-838, a group II metabotropic glutamate receptor antagonist offers insight into pathogenesis and possible treatment options for blast-related brain injury. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".

2018-01-01·eneuro3区 · 医学

PTSD-Related Behavioral Traits in a Rat Model of Blast-Induced mTBI Are Reversed by the mGluR2/3 Receptor Antagonist BCI-838

3区 · 医学

ArticleOA

作者: McCarron, Richard M ; Perez-Garcia, Georgina ; Gandy, Sam ; Ahlers, Stephen T ; Otero-Pagan, Alena ; Tschiffely, Anna ; De Gasperi, Rita ; Gama Sosa, Miguel A ; Elder, Gregory A ; Perez, Gissel M

Battlefield blast exposure related to improvised explosive devices (IEDs) has become the most common cause of traumatic brain injury (TBI) in the recent conflicts in Iraq and Afghanistan. Mental health problems are common after TBI. A striking feature in the most recent veterans has been the frequency with which mild TBI (mTBI) and posttraumatic stress disorder (PTSD) have appeared together, in contrast to the classical situations in which the presence of mTBI has excluded the diagnosis of PTSD. However, treatment of PTSD-related symptoms that follow blast injury has become a significant problem. BCI-838 (MGS0210) is a Group II metabotropic glutamate receptor (mGluR2/3) antagonist prodrug, and its active metabolite BCI-632 (MGS0039) has proneurogenic, procognitive, and antidepressant activities in animal models. In humans, BCI-838 is currently in clinical trials for refractory depression and suicidality. The aim of the current study was to determine whether BCI-838 could modify the anxiety response and reverse PTSD-related behaviors in rats exposed to a series of low-level blast exposures designed to mimic a human mTBI or subclinical blast exposure. BCI-838 treatment reversed PTSD-related behavioral traits improving anxiety and fear-related behaviors as well as long-term recognition memory. Treatment with BCI-838 also increased neurogenesis in the dentate gyrus (DG) of blast-exposed rats. The safety profile of BCI-838 together with the therapeutic activities reported here, make BCI-838 a promising drug for the treatment of former battlefield Warfighters suffering from PTSD-related symptoms following blast-induced mTBI.

100 项与 BCI-838 相关的药物交易

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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
阿尔茨海默症	临床前	美国	BrainCells, Inc.	-
重度抑郁症	药物发现	-	BrainCells, Inc.	-
重度抑郁症	药物发现	-	Taisho Pharmaceutical Holdings Co., Ltd.	-