普可那利(Pleconaril) - 在研适应症：1型糖尿病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Picovir、Pleconaril (USAN/INN)

+ [5]

靶点-

作用机制

病毒复制抑制剂

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Oslo universitetssykehus HF

非在研机构

National Institute of Allergy & Infectious Diseases

Merck Sharp & Dohme Corp.

Sanofi

+ [3]

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

结构

分子式C18H18F3N3O3

InChIKeyKQOXLKOJHVFTRN-UHFFFAOYSA-N

CAS号153168-05-9

关联

4

项与普可那利相关的临床试验

NCT04838145 / Completed临床2期

The Diabetes Virus Detection and Intervention Trial

A randomized, double-blind, placebo-controlled study in 96 children and adolescents age 6-15 newly diagnosed with type 1 diabetes to describe the influence of antiviral treatment (Pleconaril and Ribavirin) on progression of disease and residual insulin secretion.

开始日期2018-08-30

申办/合作机构

Oslo universitetssykehus HF

EUCTR2017-004125-32-CZ / Not yet recruiting临床2期

A randomised, double blind, placebo controlled trial to evaluate the safety, efficacy and pharmakokinetics of Pleconaril as an add on to AchEI/memantine for treatment of patients with Alzheimer’s disease

开始日期2018-03-28

申办/合作机构-

NCT00394914 / Completed临床2期

A Placebo-Controlled Study of the Effects of Pleconaril Nasal Spray on Common Cold Symptoms and Asthma Exacerbations Following Rhinovirus Exposure

This is a randomized, multi-center, double-blind, placebo-controlled study evaluating the efficacy of pleconaril nasal spray in preventing asthma exacerbation and common cold symptoms in asthmatic participants exposed to picornavirus respiratory infections. Participants will be assigned treatment with pleconaril or placebo nasal spray for 7 days (14 doses). Participants will be followed for an additional 14 days.

开始日期2006-08-01

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与普可那利相关的临床结果

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100 项与普可那利相关的转化医学

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100 项与普可那利相关的专利（医药）

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162

项与普可那利相关的文献（医药）

2024-04-01·Antiviral Research

The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants

Article

作者: Wolthers, Katja C ; Kainov, Denis E ; Bjørås, Magnar ; Lysvand, Hilde ; Oksenych, Valentyn ; Ianevski, Aleksandr ; Smura, Teemu ; Tenson, Tanel ; Afset, Jan Egil ; Frøysa, Irene Trøen ; Schjelderup Nilsen, Hans-Johnny ; Galabov, Angel S ; Sridhar, Adithya ; Zusinaite, Eva ; Kurg, Reet ; Calitz, Carlemi ; Stoyanova, Adelina ; Høyer, Erling

Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for these infections are limited, underscoring the urgent need for effective therapeutic strategies. To find better treatment option we analyzed toxicity and efficacy of 12 known broad-spectrum anti-enterovirals both individually and in combinations against different enteroviruses in vitro. We identified several novel, synergistic two-drug and three-drug combinations that demonstrated significant inhibition of enterovirus infections in vitro. Specifically, the triple-drug combination of pleconaril, rupintrivir, and remdesivir exhibited remarkable efficacy against echovirus (EV) 1, EV6, EV11, and coxsackievirus (CV) B5, in human lung epithelial A549 cells. This combination surpassed the effectiveness of single-agent or dual-drug treatments, as evidenced by its ability to protect A549 cells from EV1-induced cytotoxicity across seven passages. Additionally, this triple-drug cocktail showed potent antiviral activity against EV-A71 in human intestinal organoids. Thus, our findings highlight the therapeutic potential of the pleconaril-rupintrivir-remdesivir combination as a broad-spectrum treatment option against a range of enterovirus infections. The study also paves the way towards development of strategic antiviral drug combinations with virus family coverage and high-resistance barriers.

2024-02-01·Antiviral Research

Molecular mechanism of rhinovirus escape from the Pyrazolo[3,4-d]pyrimidine capsid-binding inhibitor OBR-5-340 via mutations distant from the binding pocket: Derivatives that brake resistance

Article

作者: Makarov, Vadim ; Richter, Martina ; Döring, Kristin ; Schmidtke, Michaela ; Kazakova, Elena ; Egorova, Anna ; Blaas, Dieter ; Khrenova, Maria ; Riabova, Olga

Rhinoviruses (RVs) cause the common cold. Attempts at discovering small molecule inhibitors have mainly concentrated on compounds supplanting the medium chain fatty acids residing in the sixty icosahedral symmetry-related hydrophobic pockets of the viral capsid of the Rhinovirus-A and -B species. High-affinity binding to these pockets stabilizes the capsid against structural changes necessary for the release of the ss(+) RNA genome into the cytosol of the host cell. However, single-point mutations may abolish this binding. RV-B5 is one of several RVs that are naturally resistant against the well-established antiviral agent pleconaril. However, RV-B5 is strongly inhibited by the pyrazolopyrimidine OBR-5-340. Here, we report on isolation and characterization of RV-B5 mutants escaping OBR-5-340 inhibition and show that substitution of amino acid residues not only within the binding pocket but also remote from the binding pocket hamper inhibition. Molecular dynamics network analysis revealed that strong inhibition occurs when an ensemble of several sequence stretches of the capsid proteins enveloping OBR-5-340 move together with OBR-5-340. Mutations abrogating this dynamic, regardless of whether being localized within the binding pocket or distant from it result in escape from inhibition. Pyrazolo [3,4-d]pyrimidine derivatives overcoming OBR-5-340 escape of various RV-B5 mutants were identified. Our work contributes to the understanding of the properties of capsid-binding inhibitors necessary for potent and broad-spectrum inhibition of RVs.

2023-11-01·Nature Medicine1区 · 医学

Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial

1区 · 医学

Article

作者: Ludvigsson, Johnny ; Roald, Trine ; Hanssen, Kristian F ; Hessel, Trine Witzner ; Mørk, Freja Barrett ; Lindblom, Nina ; Hyöty, Heikki ; Ponzi, Erica ; Westman, Jacob ; Johannesen, Jesper ; Krogvold, Lars ; Barker, Peter ; Mynarek, Ida Maria ; Dahl-Jørgensen, Knut

AbstractPrevious studies showed a low-grade enterovirus infection in the pancreatic islets of patients with newly diagnosed type 1 diabetes (T1D). In the Diabetes Virus Detection (DiViD) Intervention, a phase 2, placebo-controlled, randomized, parallel group, double-blind trial, 96 children and adolescents (aged 6–15 years) with new-onset T1D received antiviral treatment with pleconaril and ribavirin (n = 47) or placebo (n = 49) for 6 months, with the aim of preserving β cell function. The primary endpoint was the mean stimulated C-peptide area under the curve (AUC) 12 months after the initiation of treatment (less than 3 weeks after diagnosis) using a mixed linear model. The model used longitudinal log-transformed serum C-peptide AUCs at baseline, at 3 months, 6 months and 1 year. The primary endpoint was met with the serum C-peptide AUC being higher in the pleconaril and ribavirin treatment group compared to the placebo group at 12 months (average marginal effect = 0.057 in the linear mixed model; 95% confidence interval = 0.004–0.11, P = 0.037). The treatment was well tolerated. The results show that antiviral treatment may preserve residual insulin production in children and adolescent with new-onset T1D. This provides a rationale for further evaluating antiviral strategies in the prevention and treatment of T1D. European Union Drug Regulating Authorities Clinical Trials identifier: 2015-003350-41.

100 项与普可那利相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D05528	普可那利	J05AX06	DB05105

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
哮喘	临床前	-	Merck Sharp & Dohme Corp.	2006-08-01
肠道病毒感染	临床前	加拿大	National Institute of Allergy & Infectious Diseases	2001-06-27
肠道病毒感染	临床前	美国	National Institute of Allergy & Infectious Diseases	2001-06-27
全身炎症反应综合征	临床前	加拿大	National Institute of Allergy & Infectious Diseases	2001-06-27
全身炎症反应综合征	临床前	美国	National Institute of Allergy & Infectious Diseases	2001-06-27
细小RNA病毒科感染	临床前	-	Antivirus Therapeutics, Inc.	-
细小RNA病毒科感染	药物发现	-	Merck Sharp & Dohme Corp.	-
细小RNA病毒科感染	药物发现	-	Sanofi	-
细小RNA病毒科感染	药物发现	-	ViroPharma Incorporated	-
细小RNA病毒科感染	药物发现	-	Shire Pharmaceuticals Services Ltd.	-

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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


NCT04838145 (EudraCT number2015-003350-41, EASD2023)	临床2期	1型糖尿病 C-peptide level	96	Pleconaril and Ribavirin	糧鏇淵鹹淵鏇衊範憲齋(糧憲蓋艱壓蓋鏇製觸構) = 窪膚壓醖獵餘獵淵鑰鹽糧鑰簾顧願窪遞範憲鹽 (糧膚願餘製鏇顧積醖構 ) 更多	积极	2023-10-04
				Placebo	願齋網艱顧壓遞築襯願(構網醖衊範範壓網壓築) = 蓋夢網鏇鬱膚襯獵淵鹹憲範淵衊蓋選積蓋繭鏇 (壓窪觸獵鏇鏇壓範製構 )