MW-151(MW-151) - 药物靶点：CCL2 x CCL5_在研适应症：中毒_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

CCL2 x CCL5

作用机制

CCL2抑制剂(C-C基序趋化因子-2抑制剂)、CCL5抑制剂(C-C基序趋化因子-5抑制剂)

治疗领域

其他疾病

在研适应症

中毒

非在研适应症

阿尔茨海默症创伤性脑损伤认知障碍+ [2]

原研机构

University of Kentucky

在研机构

University of Kentucky

非在研机构

National Institute on Aging

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

2

项与 MW-151 相关的临床试验

NCT05417282 / Recruiting临床1期

Safety and Tolerability of MW151 Administered With Whole-brain Radiotherapy in Patients With Intracranial Metastases

HYPOTHESIS: MW151 intervention during whole-brain radiotherapy for intracranial metastases is safe and will mitigate neurocognitive decline.
RATIONALE: There is non-clinical evidence that MW151 reduces brain inflammation and improves neurocognitive outcomes in animal models of radiation therapy induced cognitive dysfunction, and in animal models of other CNS disorders.
PURPOSE: This feasibility trial will study whether MW151 mitigates neurocognitive decline following whole-brain radiotherapy in adult patients with intracranial metastases from solid tumors.

开始日期2022-07-01

申办/合作机构

ImmunoChem Therapeutics, LLC

[+2]

NCT04120233 / Completed临床1期IIT

A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to Healthy Volunteers

MW01-2-151SRM (=MW151), a small molecule, is being developed for the treatment of cognitive disorders. The development program is based on nonclinical evidence that MW151 improves neurocognitive outcomes in animal models of radiation-induced cognitive impairment, Alzheimer's disease, and other central nervous system (CNS) disorders.
The present study will provide safety and pharmacokinetic (PK) information on single ascending doses to support decisions for continued clinical development.

开始日期2019-10-22

申办/合作机构

University of Kentucky

[+2]

100 项与 MW-151 相关的临床结果

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100 项与 MW-151 相关的转化医学

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100 项与 MW-151 相关的专利（医药）

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8

项与 MW-151 相关的文献（医药）

2015-12-01·Journal of Neuroinflammation1区 · 医学

Attenuation of traumatic brain injury-induced cognitive impairment in mice by targeting increased cytokine levels with a small molecule experimental therapeutic

1区 · 医学

ArticleOA

作者: Webster, Scott J ; Morton, Jonathan E ; Van Eldik, Linda J ; Goulding, Danielle S ; Watterson, D Martin ; Bachstetter, Adam D

BACKGROUNDEvidence from clinical studies and preclinical animal models suggests that proinflammatory cytokine overproduction is a potential driving force for pathology progression in traumatic brain injury (TBI). This raises the possibility that selective targeting of the overactive cytokine response, a component of the neuroinflammation that contributes to neuronal dysfunction, may be a useful therapeutic approach. MW151 is a CNS-penetrant, small molecule experimental therapeutic that selectively restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis. We previously reported that MW151 administered post-injury (p.i.) is efficacious in a closed head injury (CHI) model of diffuse TBI in mice. Here we test dose dependence of MW151 to suppress the target mechanism (proinflammatory cytokine up-regulation), and explore the therapeutic window for MW151 efficacy.METHODSWe examined suppression of the acute cytokine surge when MW151 was administered at different times post-injury and the dose-dependence of cytokine suppression. We also tested a more prolonged treatment with MW151 over the first 7 days post-injury and measured the effects on cognitive impairment and glial activation.RESULTSMW151 administered up to 6 h post-injury suppressed the acute cytokine surge, in a dose-dependent manner. Administration of MW151 over the first 7 days post-injury rescues the CHI-induced cognitive impairment and reduces glial activation in the focus area of the CHI.CONCLUSIONSOur results identify a clinically relevant time window post-CHI during which MW151 effectively restores cytokine production back towards normal, with a resultant attenuation of downstream cognitive impairment.

2015-04-22·The Journal of Neuroscience1区 · 医学

Closed Head Injury in an Age-Related Alzheimer Mouse Model Leads to an Altered Neuroinflammatory Response and Persistent Cognitive Impairment

1区 · 医学

Article

作者: Van Eldik, Linda J ; Watterson, D Martin ; Bachstetter, Adam D ; Webster, Scott J

Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal neuroinflammatory changes after TBI in an AD model, the APP/PS1 knock-in (KI) mouse. Discrete temporal aspects of astrocyte, cytokine, and chemokine responses in the injured KI mice were delayed compared with the injured wild-type mice, with a peak neuroinflammatory response in the injured KI mice occurring at 7 d after injury. The neuroinflammatory responses were more persistent in the injured KI mice, leading to a chronic neuroinflammation. At late time points after injury, KI mice exhibited a significant impairment in radial arm water maze performance compared with sham KI mice or injured wild-type mice. Intervention with a small-molecule experimental therapeutic (MW151) that selectively attenuates proinflammatory cytokine production yielded improved cognitive behavior outcomes, consistent with a link between neuroinflammatory responses and altered risk for AD-associated pathology changes with head injury.

2014-09-24·The Journal of Neuroscience1区 · 医学

An Anti-Neuroinflammatory That Targets Dysregulated Glia Enhances the Efficacy of CNS-Directed Gene Therapy in Murine Infantile Neuronal Ceroid Lipofuscinosis

1区 · 医学

Article

作者: Cooper, Jonathan D ; Sands, Mark S ; Pearse, Yewande ; Dearborn, Joshua T ; Watterson, D Martin ; Roberts, Marie S ; Augner, David P ; Macauley, Shannon L ; Fowler, Stephen C ; Shyng, Charles ; Wong, Andrew M S

Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited neurodegenerative lysosomal storage disease (LSD) caused by a deficiency in palmitoyl protein thioesterase-1 (PPT1). Studies inPpt1−/−mice demonstrate that glial activation is central to the pathogenesis of INCL. Astrocyte activation precedes neuronal loss, while cytokine upregulation associated with microglial reactivity occurs before and concurrent with neurodegeneration. Therefore, we hypothesized that cytokine cascades associated with neuroinflammation are important therapeutic targets for the treatment of INCL. MW01–2-151SRM (MW151) is a blood–brain barrier penetrant, small-molecule anti-neuroinflammatory that attenuates glial cytokine upregulation in models of neuroinflammation such as traumatic brain injury, Alzheimer's disease, and kainic acid toxicity. Thus, we used MW151, alone and in combination with CNS-directed, AAV-mediated gene therapy, as a possible treatment for INCL. MW151 alone decreased seizure susceptibility. When combined with AAV-mediated gene therapy, treated INCL mice had increased life spans, improved motor performance, and eradication of seizures. Combination-treated INCL mice also had decreased brain atrophy, astrocytosis, and microglial activation, as well as intermediary effects on cytokine upregulation. These data suggest that MW151 can attenuate seizure susceptibility but is most effective when used in conjunction with a therapy that targets the primary genetic defect.

100 项与 MW-151 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
中毒	临床1期	-	University of Kentucky	-
创伤性脑损伤	临床前	美国	-	2019-10-31
药物中毒	临床前	美国	National Institute on Aging	2019-10-22
认知障碍	临床前	美国	-	2019-09-29
阿尔茨海默症	临床前	美国	-	2019-09-21
多发性硬化症	临床前	美国	-	2019-09-20

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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


NCT04120233 (CTgov)	临床1期	药物中毒	40	Placebo (Placebo)	淵艱餘餘夢鏇獵餘繭遞(積選淵艱網獵製簾艱製) = 餘艱顧鏇願憲憲築觸齋餘遞築獵繭蓋選構糧獵 (築醖築構構憲遞願鹹糧, 網膚鹽範醖遞鹽膚繭餘 ~ 鏇鏇蓋觸遞襯範簾鑰選) 更多	-	2022-12-30
				MW151, 10mg (Dose 1)	淵艱餘餘夢鏇獵餘繭遞(積選淵艱網獵製簾艱製) = 襯憲簾構鑰膚糧齋簾網餘遞築獵繭蓋選構糧獵 (築醖築構構憲遞願鹹糧, 膚遞繭願夢簾廠網觸築 ~ 憲鹽艱衊膚顧夢廠夢鹹) 更多