NRP-2945(NRP-2945) - 药物靶点：CXCR4_在研适应症：癫痫，颞叶癫痫，Lennox-Gastaut综合征_专利_临床

概要

基本信息

药物类型

合成多肽

别名

靶点

CXCR4

作用机制

CXCR4调节剂(C-X-C基序趋化因子受体4调节剂)

治疗领域

神经系统疾病遗传病与畸形其他疾病

在研适应症

癫痫颞叶癫痫Lennox-Gastaut综合征

非在研适应症

肌萎缩侧索硬化天使综合征失神发作+ [2]

原研机构

Neuren Pharmaceuticals Ltd.

在研机构

CuroNZ Ltd.

Neuren Pharmaceuticals Ltd.

非在研机构-

最高研发阶段临床2期

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C41H75N21O11

InChIKeyNSVUYPMUSKVTRT-FRSCJGFNSA-N

CAS号1145786-97-5

序列信息

Sequence Code 9880459

关联

2

项与 NRP-2945 相关的临床试验

ACTRN12618001506280 / Completed临床2期

A Phase 2a, single-blind, placebo-controlled safety and efficacy study of two doses of NRP2945 in patients showing drug-resistant typical absence epilepsy as a form of their genetic, generalized epilepsy pattern

开始日期2018-12-11

申办/合作机构-

ACTRN12617000377336 / Recruiting临床1期

A Double-blind, Randomised, Placebo-controlled Study to Determine the Safety, Pharmacokinetics and Maximum Tolerated Dose of NRP2945 In Healthy Adult Volunteers.

开始日期2017-03-14

申办/合作机构-

100 项与 NRP-2945 相关的临床结果

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100 项与 NRP-2945 相关的转化医学

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100 项与 NRP-2945 相关的专利（医药）

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4

项与 NRP-2945 相关的文献（医药）

2023-09-01·CNS Drugs

New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development

Review

作者: White, H Steve ; Perucca, Emilio ; Bialer, Meir

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the modulation of neuronal excitability, and a disruption of GABAergic transmission contributes to the pathogenesis of some seizure disorders. Although many currently available antiseizure medications do act at least in part by potentiating GABAergic transmission, there is an opportunity for further research aimed at developing more innovative GABA-targeting therapies. The present article summarises available evidence on a number of such treatments in clinical development. These can be broadly divided into three groups. The first group consists of positive allosteric modulators of GABA_A receptors and includes Staccato^® alprazolam (an already marketed benzodiazepine being repurposed in epilepsy as a potential rescue inhalation treatment for prolonged and repetitive seizures), the α2/3/5 subtype-selective agents darigabat and ENX-101, and the orally active neurosteroids ETX155 and LPCN 2101. A second group comprises two drugs already marketed for non-neurological indications, which could be repurposed as treatments for seizure disorders. These include bumetanide, a diuretic agent that has undergone clinical trials in phenobarbital-resistant neonatal seizures and for which the rationale for further development in this indication is under debate, and ivermectin, an antiparasitic drug currently investigated in a randomised double-blind trial in focal epilepsy. The last group comprises a series of highly innovative therapies, namely GABAergic interneurons (NRTX-001) delivered via stereotactic cerebral implantation as a treatment for mesial temporal lobe epilepsy, an antisense oligonucleotide (STK-001) aimed at upregulating NaV1.1 currents and restoring the function of GABAergic interneurons, currently tested in a trial in patients with Dravet syndrome, and an adenoviral vector-based gene therapy (ETX-101) scheduled for investigation in Dravet syndrome. Another agent, a subcutaneously administered neuroactive peptide (NRP2945) that reportedly upregulates the expression of GABA_A receptor α and β subunits is being investigated, with Lennox-Gastaut syndrome and other epilepsies as proposed indications. The diversity of the current pipeline underscores a strong interest in the GABA system as a target for new treatment development in epilepsy. To date, limited clinical data are available for these investigational treatments and further studies are required to assess their potential value in addressing unmet needs in epilepsy management.

2021-06-01·European Journal of Pharmacology3区 · 医学

Anti-epileptogenic effect of NRP2945 in the pilocarpine model of temporal lobe epilepsy

3区 · 医学

Article

作者: Falcicchia, Chiara ; Lovisari, Francesca ; Soukupova, Marie ; Ingusci, Selene ; Marino, Pietro ; Sieg, Frank ; Guarino, Annunziata ; Thomas, Mark ; Simonato, Michele

Innovative therapeutic strategies are highly needed to tackle the major medical needs of epilepsy, like prevention of epilepsy development in at-risk individuals, treatment of severe and drug-resistant forms, control of co-morbidities. The Neural Regeneration Peptide NRP2945 (a peptidomimetic analogue of the human CAPS-2 protein) has been recently found to exert many potentially anti-epileptic effects, for example increased neuronal survival and differentiation. In the present study, we tested the effects of NRP2945 on the development of epilepsy (epileptogenesis) and on chronic, spontaneous seizures, by using the pilocarpine model of temporal lobe epilepsy. We found that NRP2945 exerts a robust anti-epileptogenic effect, reducing the frequency of spontaneous seizures, exerting a significant neuroprotective effect and attenuating anxiety-like behaviors and cognitive impairment. These effects appear to depend on modulation of the epileptogenesis process and not on seizure suppression, because NRP2945 did not reduce frequency or duration of spontaneous seizures when administered to already epileptic animals. These findings may form the basis for a preventive therapy for individuals at-risk of developing epilepsy.

2017-07-01·Neurochemical Research3区 · 医学

Disease-Modifying Effects of Neural Regeneration Peptide 2945 in the GAERS Model of Absence Epilepsy

3区 · 医学

Article

作者: Jones, Nigel C ; van der Hart, Marieke ; Dezsi, Gabi ; Thomas, Mark ; O'Brien, Terence J ; Sieg, Frank

Epilepsy is a common neurological condition characterised by spontaneous recurrent seizures. Current anti-epileptic drugs are only effective and tolerated in ~70% of patients, leaving a substantial proportion of patients untreated. As such, there is a pressing need to develop new therapies. We assessed the anti-seizure activity of Neural Regeneration Peptide 2945 (NRP 2945) in the GAERS model of absence epilepsy. Drug effects on seizures were assessed using two study designs. Male adult GAERS were implanted with EEG electrodes to measure seizure frequency. The first study compared the effects of acute sc injection of vehicle, NRP 10 µg/kg, NRP 20 µg/kg, and controlled against the active comparator Valproaic acid (200 mg/kg). In the second study, animals received one of four treatments for 4 weeks: vehicle, NRP 60 µg/kg/day, NRP 120 µg/kg/day (delivered by continuous infusion) or NRP 20 µg/kg sc injected every second day (e.s.d). In the acute study, we found significant (p < 0.01) anti-seizure effects in animals treated with NRP2945 (20 µg/kg) and VPA, with NRP2945 slightly more efficacious, despite the 70,000 times lower molar dosage. In the chronic study, animals receiving 120 µg/kg/day and NRP 20 µg/kg e.s.d had significantly fewer seizures (p < 0.001), compared with vehicle. These effects were sustained for at least 10 days after drug treatment had ceased, indicative of disease-modifying activity. We demonstrate sustained anti-seizure effects of NRP2945, a potent small molecule peptide which enters the brain and is devoid of adverse effects. Early stage first-in-man trials have been initiated for subcutaneously delivered NRP2945 which is a promising step to providing therapeutic benefits for refractory epilepsy patients.

100 项与 NRP-2945 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
癫痫	临床2期	-	Neuren Pharmaceuticals Ltd.	-
颞叶癫痫	临床2期	-	CuroNZ Ltd.	-
Lennox-Gastaut综合征	临床2期	-	CuroNZ Ltd.	-
多发性硬化症	临床1期	新西兰	CuroNZ Ltd.	-
天使综合征	药物发现	新西兰	CuroNZ Ltd.	2020-04-17
Rett综合征	药物发现	新西兰	CuroNZ Ltd.	2020-03-17
肌萎缩侧索硬化	药物发现	新西兰	CuroNZ Ltd.	2020-03-07
失神发作	药物发现	澳大利亚	CuroNZ Ltd.	2018-12-11