ONO-2952(ONO-2952) - 药物靶点：TSPO_在研适应症：多发性硬化症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

TSPO

作用机制

TSPO抑制剂(TSPO蛋白抑制剂)

治疗领域

免疫系统疾病神经系统疾病其他疾病

在研适应症

多发性硬化症

非在研适应症

肠易激综合征疼痛

原研机构

Ono Pharmaceutical Co., Ltd.

在研机构

Ono Pharmaceutical Co., Ltd.

非在研机构

Ono Pharma USA, Inc.

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C22H20ClFN2O2

InChIKeyZBQMTQGDBFZUBG-NRFANRHFSA-N

CAS号895169-20-7

关联

5

项与 ONO-2952 相关的临床试验

NCT01887002 / Terminated临床2期

A Phase 2, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Effects of ONO-2952 on Pain Perception Produced by Rectal Distention in Female Subjects With Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) (RESTORE)

The objective is to evaluate whether ONO-2952 modulates visceral pain perception produced by rectal distention in female patients with IBS-D

开始日期2013-06-01

申办/合作机构

Ono Pharma USA, Inc.

NCT01844180 / Completed临床2期

A Phase 2, Multi-center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ONO-2952 in Female Subjects With Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)

The objective of this study is to explore efficacy, safety and tolerability of ONO-2952 in female subjects with Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D).

开始日期2013-04-01

申办/合作机构

Ono Pharma USA, Inc.

NCT01613703 / Completed临床1期

Open-Label, Single-Center, Single Dose Positron Emission Topography (PET) Using [11C]PBR28 to Evaluate Brain Translocator Protein 18KDa (TSPO) Occupancy of ONO-2952 in Healthy Adult Subjects

The primary objective of this study is to evaluate the brain TSPO occupancy of ONO-2952 in healthy adult subjects after a single dose using [11C]PBR28 as a specific PET ligand for TSPO. The secondary objective is to evaluate the relationship between TSPO occupancy and the plasma concentration of ONO-2952 and to investigate the safety and tolerability of ONO-2952 in healthy subjects.

开始日期2012-08-01

申办/合作机构

Ono Pharma USA, Inc.

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100 项与 ONO-2952 相关的临床结果

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100 项与 ONO-2952 相关的转化医学

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100 项与 ONO-2952 相关的专利（医药）

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9

项与 ONO-2952 相关的文献（医药）

2021-07-01·Shock2区 · 医学

Pharmacological and Genetic Inhibition of Translocator Protein 18 kDa Ameliorated Neuroinflammation in Murine Endotoxemia Model

2区 · 医学

Article

作者: Hosokawa, Koji ; Matsumata, Miho ; Kitajima, Takashi ; Katsumata, Seishi ; Ji, Bin ; Fukuda, Shuji ; Giga, Hiroshi ; Aizawa, Hidenori ; Yamawaki, Shigeto ; Suhara, Tetsuya ; Shime, Nobuaki ; Kikutani, Kazuya

ABSTRACTSepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction associated with sepsis. The development of an effective strategy for early diagnosis and therapeutic intervention is essential for the prevention of poor prognosis of SAE. Translocator protein 18 kDa (TSPO) is a mitochondrial protein implicated in steroidogenesis and inflammatory responses. Despite accumulating evidence that implicates TSPO in the neuroinflammatory response of the central nervous system, the possible role of TSPO in SAE remains unclear. The aim of this study is to address a role of TSPO in neuroinflammation using mice 24 h after systemic injection of LPS, which consistently demonstrated microglial activation and behavioral inhibition. Quantitative polymerase chain reaction analysis revealed that hippocampal TSPO expression was induced following the systemic LPS injection, associated with an increase in pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-1β. Interestingly, pretreatment with the TSPO antagonist, ONO-2952, or germ-line deletion of the TSPO gene exhibited an anti-inflammatory effect with significant suppression of LPS-induced production of those cytokines. These effects demonstrated by the ONO-2952 or TSPO knockout were associated with significant recovery from behavioral inhibition, as shown by improved locomotor activity in the open field analysis. Histological analysis revealed that ONO-2952 pretreatment suppressed the LPS-induced activation of TSPO-expressing microglia in the hippocampus of mice. Collectively, these results suggest that TSPO plays a critical role in the SAE mouse model. Based on this finding, monitoring TSPO activity, as well as the progress of endotoxemia and its sequelae in the animal model, would deepen our understanding of the underlying molecular mechanism of SAE.

2020-01-01·Neuropharmacology2区 · 医学

Antidepressant effect of the translocator protein antagonist ONO-2952 on mouse behaviors under chronic social defeat stress

2区 · 医学

Article

作者: Katsumata, Seishi ; Yamawaki, Shigeto ; Yamawaki, Yosuke ; Kato, Takahiro A ; Ito, Hikaru ; Ohgidani, Masahiro ; Kitajima, Takashi ; Aizawa, Hidenori ; Nozaki, Kanako ; Sahin, Ezgi Hatice

In preclinical models, it has been reported that social defeat stress activates microglial cells in the CNS. Translocator protein 18 kDa (TSPO) is a mitochondrial protein expressed on microglia in the CNS that has been proposed to be a useful biomarker for brain injury and inflammation. We hypothesized that a TSPO antagonist, ONO-2952, would inhibit the neuroinflammation induced by microglial hyperactivation and associated depressive-like behaviors. An in vitro analysis showed that ONO-2952 suppressed the release of pro-inflammatory cytokines and mitochondrial reactive oxygen species in cultured microglia stimulated by lipopolysaccharide. In mice submitted to chronic social defeat stress, microglia predominantly expressed TSPO in limbic areas implicated in depressive-like behaviors, including the amygdala, ventral hippocampus and nucleus accumbens, in which an increase in the production of pro-inflammatory cytokines in vivo were associated. Treating animals with ONO-2952 during chronic social defeat stress ameliorated impairments in social avoidance and anxiety-like behaviors and suppressed pro-inflammatory cytokine production, suggesting that ONO-2952 exerted an anti-stress effect in this animal model of depression. Thus, targeting TSPO as a candidate for the development of antidepressants that reduce susceptibility to chronic stress could pave the way toward therapeutic interventions for relapse prophylaxis in depression.

2017-07-01·Synapse4区 · 医学

Brain translocator protein occupancy by ONO‐2952 in healthy adults: A Phase 1 PET study using [¹¹C]PBR28

4区 · 医学

Article

作者: Yamauchi, Akinori ; Frankle, W. Gordon ; Narendran, Rajesh ; Suto, Fumitaka ; Duffy, Kevin ; Wood, Andrew T. ; Kobayashi, Michiyoshi ; Himes, Michael L. ; Bruce, Mark ; Ohno, Tomoya ; Mitsui, Katsukuni

AbstractONO‐2952, a novel antagonist of translocator protein 18 kDa (TSPO), binds with high affinity to TSPO in rat brain and human tumor cell line membrane preparations. This study used the TSPO‐specific PET radioligand [11 C]PBR28 to confirm binding of ONO‐2952 to brain TSPO in human subjects, and evaluate brain TSPO occupancy and its relationship with ONO‐2952 plasma concentration. Sixteen healthy subjects received a single oral dose of 200, 60, 20, or 6 mg ONO‐2952 (n = 4 per dose). Two PET scans with [11 C]PBR28 were conducted ≤7 days apart: at baseline and 24 h after ONO‐2952 administration. [11 C]PBR28 regional distribution volume (VT) was derived with kinetic modeling using the arterial input function and a two tissue compartment model. Nonspecific binding (VND) was obtained on an individual basis for each subject using linear regression as the x‐intercept of the Lassen plot. The binding potential relative to VND (BPND) was derived as the difference between VT in the ROI (VT ROI) and VND, normalized to VND; BPND = (VT ROI – VND)/VND. TSPO occupancy was calculated as the change in BPND (ΔBPND) from individual's baseline scan to the on‐medication scan to the baseline BPND value. TSPO occupancy by ONO‐2952 was dose dependent between 20–200 mg, approaching saturation at 200 mg both in the whole brain and in 15 anatomic regions of interest (ROI). Estimated Ki values ranged from 24.1 to 72.2 nM. This open‐label, single‐center, single‐dose study demonstrated engagement of ONO‐2952 to brain TSPO. The relationship between pharmacokinetics and TSPO occupancy observed in this study support the hypothesis that ONO‐2952 could potentially modulate neurosteroid production by binding to brain TSPO.

100 项与 ONO-2952 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14802

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
疼痛	临床前	美国	Ono Pharma USA, Inc.	2013-06-01
肠易激综合征	临床前	美国	Ono Pharma USA, Inc.	2013-04-01
多发性硬化症	临床前	日本	Ono Pharmaceutical Co., Ltd.	-