PRI-002(PRI-002) - 药物靶点：APP x N-type calcium channel_在研适应症：阿尔茨海默症，轻度认知障碍_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Contraloid、Contraloid Acetate

+ [1]

靶点

APP x N-type calcium channel

作用机制

APP抑制剂(β-淀粉状蛋白A4抑制剂)、N-type calcium channel抑制剂(Calcium channel inhibitor N-types inhibitors)

治疗领域

神经系统疾病其他疾病

在研适应症

阿尔茨海默症轻度认知障碍

非在研适应症-

原研机构

Priavoid GmbH

在研机构

Priavoid GmbH

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-

结构

分子式C55H78O4

InChIKeyBINXWQZTCIKYFR-UWKHKGTHSA-N

CAS号1271740-13-6

关联

5

项与 PRI-002 相关的临床试验

CTIS2022-503148-41-00 / Recruiting

Randomised, double-blind, placebo-controlled study to assess safety and efficacy of PRI-002 in patients with MCI or mild dementia due to Alzheimer’s disease (AD) - PRI-002-04

开始日期2024-01-09

申办/合作机构

Prinnovation GmbH

NCT06182085 / Recruiting临床2期

Randomised, Double-blind, Placebo-controlled Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD) (PRImus-AD)

Alzheimer's disease (AD) is the most common form of dementia. In the brains of people with AD, certain small substances stick together. This leads to changes in thinking and behaviour. The company PRInnovation is developing a new treatment for Alzheimer's disease, called PRI-002. It is thought that PRI-002 can cut the sticked substances back into small pieces. That would reduce the effects of Alzheimer's disease. In the current study the investigators examine whether PRI-002 is safe and effective in participants with mild cognitive impairment (MCI) or mild dementia due to AD.

开始日期2023-12-01

申办/合作机构

Prinnovation GmbH

[+2]

NCT04711486 / Completed临床1期IIT

A Single-centre, Randomized, Placebo-controlled, Double-blind, Phase 1b Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Contraloid Acetate in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease

Patients with mild cognitive impairment due to Alzheimer's disease (MCI due to AD) are at high risk to develop Alzheimer´s dementia. The therapeutic agent Contraloid has the potential to influence the chronic neurodegenerative process of AD. As Contraloid was so far only administered to healthy subjects, the rational of the proposed study is first to collect safety data in patients diagnosed with MCI due to AD, as the absorption, distribution, metabolism and excretion processes may be altered by disease, aging, comorbidities and concomitant drug therapies. Additionally, the design of a subsequent phase II study will be based on the data of this study. The results of the exploratory analyses will enable power calculations and the identification of the most useful and reliable biomarkers for the subsequent proof of concept phase II study.

开始日期2020-12-08

申办/合作机构

Charité - Universitätsmedizin Berlin

[+1]

100 项与 PRI-002 相关的临床结果

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100 项与 PRI-002 相关的转化医学

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100 项与 PRI-002 相关的专利（医药）

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38

项与 PRI-002 相关的文献（医药）

2024-06-01·British Journal of Pharmacology

An orally available Ca_v2.2 calcium channel inhibitor for the treatment of neuropathic pain

Article

作者: Wollert, Esther ; Beck-Sickinger, Annette G ; Jürgens, Dagmar ; Guzman, Gustavo A ; Klöcker, Nikolaj ; Stark, Holger ; Willbold, Dieter ; Gering, Ian ; Breitkreutz, Jörg ; Kutzsche, Janine ; Willuweit, Antje ; Hidalgo, Patricia ; Kletke, Olaf

AbstractBackground and PurposeNeuropathic pain affects up to 10% of the global population and is caused by an injury or a disease affecting the somatosensory, peripheral, or central nervous system. NP is characterized by chronic, severe and opioid‐resistant properties. Therefore, its clinical management remains very challenging. The N‐type voltage‐gated calcium channel, Cav2.2, is a validated target for therapeutic intervention in chronic and neuropathic pain. The conotoxin ziconotide (Prialt®) is an FDA‐approved drug that blocks Cav2.2 channel but needs to be administered intrathecally. Thus, although being principally efficient, the required application route is very much in disfavour.Experimental Approach and Key ResultsHere, we describe an orally available drug candidate, RD2, which competes with ziconotide binding to Cav2.2 at nanomolar concentrations and inhibits Cav2.2 almost completely reversible. Other voltage‐gated calcium channel subtypes, like Cav1.2 and Cav3.2, were affected by RD2 only at concentrations higher than 10 μM. Data from sciatic inflammatory neuritis rat model demonstrated the in vivo proof of concept, as low‐dose RD2 (5 mg·kg‐1) administered orally alleviated neuropathic pain compared with vehicle controls. High‐dose RD2 (50 mg·kg‐1) was necessary to reduce pain sensation in acute thermal response assessed by the tail flick test.Conclusions and ImplicationsTaken together, these results demonstrate that RD2 has antiallodynic properties. RD2 is orally available, which is the most convenient application form for patients and caregivers. The surprising and novel result from standard receptor screens opens the room for further optimization into new promising drug candidates, which address an unmet medical need.

2024-04-01·Archives of Microbiology

Biotransformation approach to produce rare ginsenosides F1, compound Mc1, and Rd2 from major ginsenosides

Article

作者: Xie, Nengzhong ; Chen, Yanchi ; Meng, Lijun ; Diao, Mengxue ; Li, Jianxiu

The stems and leaves of Panax notoginseng contain high saponins, but they are often discarded as agricultural waste. In this study, the predominant ginsenosides Rg1, Rc, and Rb2, presented in the stems and leaves of ginseng plants, were biotransformed into value-added rare ginsenosides F1, compound Mc1 (C-Mc1), and Rd2, respectively. A fungal strain YMS6 (Penicillium sp.) was screened from the soil as a biocatalyst with high selectivity for the deglycosylation of major ginsenosides. Under the optimal fermentation conditions, the yields of F1, C-Mc1, and Rd2 were 97.95, 68.64, and 79.58%, respectively. This study provides a new microbial resource for the selective conversion of protopanaxadiol-type and protopanaxatriol-type major saponins into rare ginsenosides via the whole-cell biotransformation and offers a solution for the better utilization of P. notoginseng waste.

2023-08-07·Molecular pharmaceutics

Automated Synthesis and Preclinical Evaluation of Optimized Integrin α6-Targeted Positron Emission Tomography Imaging of Pancreatic Cancer.

Article

作者: Ye, Jiacong ; Feng, Guokai ; Yu, Chunjing ; He, Huihui ; Li, Qingbo ; Lou, Kequan ; Fu, Haitian ; Chen, Liping

Integrin α6 has been considered a promising biomarker, is overexpressed in many tumors, and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we identified a novel high-affinity integrin α6-targeted peptide named RD₂ (Arg-Trp-Tyr-Asp-PEG4)₂-Lys-Lys and developed a ¹⁸F-radiolabeled peptide tracer ([¹⁸F]-AlF-NOTA-RD₂) and evaluated its potential application in positron emission tomography (PET) imaging of pancreatic cancer. [¹⁸F]-AlF-NOTA-RD₂ was produced using GMP (Good Manufacturing Practice of Medical Products)-compliant automatic radiosynthesis on a single GE FASTLab2 cassette-type synthesis module. The stability of [¹⁸F]-AlF-NOTA-RD₂ was analyzed in phosphate-buffered saline (PBS) and fetal bovine serum (FBS). The cell uptake assay of the tracer was assessed using PANC-1 cells. In addition, small-animal PET imaging and biodistribution studies of [¹⁸F]-AlF-NOTA-RD₂ were performed in pancreatic cancer subcutaneous tumor-bearing mice. The PET tracer [¹⁸F]-AlF-NOTA-RD₂ was obtained with a radiochemical yield of 23.7 ± 4.7%, radiochemical purity of >99%, and molar activity of 165.7 ± 59.1 GBq/μmol. [¹⁸F]-AlF-NOTA-RD₂ exhibited good in vitro stability in PBS and FBS. LogP octanol water value for the tracer was -2.28 ± 0.05 (n = 3). The binding affinity of RD₂ to the integrin α6 protein (K_d = 0.13 ± 3.65 μM, n = 3) was significantly higher than that of the RWY (CRWYDENAC) (K_d = 6.97 ± 1.44 μM, n = 3). Small-animal PET imaging and biodistribution also revealed that [¹⁸F]-AlF-NOTA-RD₂ displayed rapid and good tumor uptake and lower liver background uptake in PANC-1 tumor-bearing mice. [¹⁸F]-AlF-NOTA-RD₂ showed significant radioactivity accumulation in tumors and was successfully blocked by NOTA-RD₂. Compared with [¹⁸F]-FDG, [¹⁸F]-AlF-NOTA-RD₂ PET imaging and biodistribution studies in PANC-1 xenograft tumor-bearing mice confirmed a good tumor-to-muscle ratio (8.69 ± 2.03 vs 1.41 ± 0.23, respectively) at 0.5 h and (2.99 ± 3.02 vs 1.43 ± 0.17, respectively) at 1 h post injection. Autoradiography of human pancreatic cancer tumor tissues further confirmed high accumulation of [¹⁸F]-AlF-NOTA-RD₂. In summary, we developed an optimized integrin α6-targeted imaging tracer and obtained high radioactivity products with a cassette-type synthesis module; moreover, the tracer exhibited good binding affinity with integrin α6 and good target specificity for PANC-1 cells in xenograft pancreatic tumor-bearing mice, demonstrating its promising application as a noninvasive PET radiotracer of integrin α6 expression in pancreatic cancer.

1

项与 PRI-002 相关的新闻（医药）

2019-05-12

·BioPortfolio

Alzheimer therapy from Jülich passes another important test

(Forschungszentrum Juelich) The Alzheimer drug candidate PRI-002 developed at Forschungszentrum Jülich has successfully completed Phase I of clinical research involving healthy volunteers. When administered daily over a period of four weeks, the active substance proved to be safe for use in humans. The next milestone will be the proof of efficacy in patients in clinical Phase II.

100 项与 PRI-002 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2期	荷兰	Priavoid GmbH	2023-12-01
阿尔茨海默症	临床2期	德国	Priavoid GmbH	2023-12-01
阿尔茨海默症	临床2期	西班牙	Priavoid GmbH	2023-12-01
阿尔茨海默症	临床2期	捷克	Priavoid GmbH	2023-12-01
轻度认知障碍	临床2期	西班牙	Priavoid GmbH	2023-12-01
轻度认知障碍	临床2期	波兰	Priavoid GmbH	2023-12-01
轻度认知障碍	临床2期	意大利	Priavoid GmbH	2023-12-01
轻度认知障碍	临床2期	捷克	Priavoid GmbH	2023-12-01
轻度认知障碍	临床2期	德国	Priavoid GmbH	2023-12-01
轻度认知障碍	临床2期	荷兰	Priavoid GmbH	2023-12-01

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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


CTAD2022	临床1期	Aβ1-42 \| Aβ oligomers	20	RD2	艱觸衊壓夢壓鏇範夢簾(餘齋製餘鹽衊蓋構願艱) = 13 patients reported in total 27 adverse events while no serious adverse event was noted. There was no statistical difference regarding adverse events between treatment and placebo. In contrast to reported anti- Aβ-antibody-treatments, no ARIA events have been observed. 醖夢簾構廠簾顧製選壓 (範鬱築夢窪觸繭簾艱醖 ) 更多	积极	2022-12-03
				Placebo