(Narlaprevir) - 药物靶点：NS3/NS4A_在研适应症：丙型肝炎_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Arlansa、Narlaprevir (USAN/INN)

靶点

NS3/NS4A

作用机制

NS3/NS4A抑制剂(丙型肝炎病毒NS3/NS4A丝氨酸蛋白酶抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

Merck Sharp & Dohme Corp.Merck GmbH

最高研发阶段批准上市

首次获批日期

俄罗斯 (2016-06-03),

丙型肝炎

最高研发阶段(中国)-

特殊审评-

登录后查看首次获批时间轴

结构

分子式C36H61N5O7S

InChIKeyRICZEKWVNZFTNZ-LFGITCQGSA-N

CAS号865466-24-6

关联

9

项与 Narlaprevir 相关的临床试验

NCT04246723 / Completed临床2期

Efficacy and Safety of All-Oral Combination of Narlaprevir/Ritonavir and Sofosbuvir in Treatment-naïve Patients With Chronic Hepatitis C Genotype 1

Multicenter, open-label, phase II safety and efficacy study of all-oral combination of narlaprevir/ritonavir and sofosbuvir in Treatment-naïve Patients with Chronic Hepatitis C Genotype 1.

开始日期2019-05-06

申办/合作机构

R-Pharm JSC

[+1]

NCT03485846 / Completed临床2期

Multicenter, Open-label, Phase II Safety and Efficacy Study of All-oral Combination Narlaprevir/Ritonavir and Daclatasvir Administered for 12 Weeks in Patients With Genotype 1b Chronic Hepatitis C

The purpose of this study is to confirm that combination of Narlaprevir, Ritonavir and Daclatasvir is safe and highly effective regimen in treatment-naїve patients with chronic hepatitis C (HCV) genotype 1b infection.

开始日期2017-11-27

申办/合作机构

R-Pharm JSC

[+1]

NCT03537404 / Completed临床1期

A Drug Interaction Study to Assess the Pharmacokinetics of Narlaprevir and Antiretroviral Drugs

The study purpose is to evaluate the potential for a pharmacokinetic drug-drug interaction, safety and tolerability when Narlaprevir, Ritonavir (used as a metabolic inhibitor) and Tenofovir disoproxil fumarate (part 1) and Narlaprevir, Ritonavir and Raltegravir (part 2) are administered in combination to healthy volunteers.

开始日期2017-04-24

申办/合作机构

R-Pharm JSC

[+1]

100 项与 Narlaprevir 相关的临床结果

登录后查看更多信息

100 项与 Narlaprevir 相关的转化医学

登录后查看更多信息

100 项与 Narlaprevir 相关的专利（医药）

登录后查看更多信息

22

项与 Narlaprevir 相关的文献（医药）

2023-09-01·Scientific African

The anti-SARS-CoV-2 activity of novel 9, 10-dihydrophenanthrene derivatives: an insight into molecular docking, ADMET analysis, and molecular dynamics simulation.

Article

作者: Errougui, Abdelkbir ; Kouali, Mhammed El ; Abchir, Oussama ; Talbi, Mohammed ; Mali, Suraj N ; Chtita, Samir ; Yamari, Imane

Originating in Wuhan, the COVID-19 pandemic wave has had a profound impact on the global healthcare system. In this study, we used a 2D QSAR technique, ADMET analysis, molecular docking, and dynamic simulations to sort and evaluate the performance of thirty-nine bioactive analogues of 9,10-dihydrophenanthrene. The primary goal of the study is to use computational approaches to create a greater variety of structural references for the creation of more potent SARS-CoV-2 3Clpro inhibitors. This strategy is to speed up the process of finding active chemicals. Molecular descriptors were calculated using 'PaDEL' and 'ChemDes' software, and then redundant and non-significant descriptors were eliminated by a module in 'QSARINS ver. 2.2.2'. Subsequently, two statistically robust QSAR models were developed by applying multiple linear regression (MLR) methods. The correlation coefficients obtained by the two models are 0.89 and 0.82, respectively. These models were then subjected to internal and external validation tests, Y-randomization, and applicability domain analysis. The best model developed is applied to designate new molecules with good inhibitory activity values against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). We also examined various pharmacokinetic properties using ADMET analysis. Then, through molecular docking simulations, we used the crystal structure of the main protease of SARS-CoV-2 (3CLpro/Mpro) in a complex with the covalent inhibitor "Narlaprevir" (PDB ID: 7JYC). We also supported our molecular docking predictions with an extended molecular dynamics simulation of a docked ligand-protein complex. We hope that the results obtained in this study can be used as good anti-SARS-CoV-2 inhibitors.

2023-04-28·Pharmaceuticals (Basel, Switzerland)

Recent Advances in Covalent Drug Discovery.

Review

作者: Cheng, Xinlai ; Schaefer, Daniel

In spite of the increasing number of biologics license applications, the development of covalent inhibitors is still a growing field within drug discovery. The successful approval of some covalent protein kinase inhibitors, such as ibrutinib (BTK covalent inhibitor) and dacomitinib (EGFR covalent inhibitor), and the very recent discovery of covalent inhibitors for viral proteases, such as boceprevir, narlaprevir, and nirmatrelvir, represent a new milestone in covalent drug development. Generally, the formation of covalent bonds that target proteins can offer drugs diverse advantages in terms of target selectivity, drug resistance, and administration concentration. The most important factor for covalent inhibitors is the electrophile (warhead), which dictates selectivity, reactivity, and the type of protein binding (i.e., reversible or irreversible) and can be modified/optimized through rational designs. Furthermore, covalent inhibitors are becoming more and more common in proteolysis, targeting chimeras (PROTACs) for degrading proteins, including those that are currently considered to be 'undruggable'. The aim of this review is to highlight the current state of covalent inhibitor development, including a short historical overview and some examples of applications of PROTAC technologies and treatment of the SARS-CoV-2 virus.

2023-04-13·Briefings in Functional Genomics

A comprehensive protein design protocol to identify resistance mutations and signatures of adaptation in pathogens

Article

作者: Tripathi, Timir ; Padhi, Aditya K.

AbstractMost pathogens mutate and evolve over time to escape immune and drug pressure. To achieve this, they alter specific hotspot residues in their intracellular proteins to render the targeted drug(s) ineffective and develop resistance. Such hotspot residues may be located as a cluster or uniformly as a signature of adaptation in a protein. Identifying the hotspots and signatures is extremely important to comprehensively understand the disease pathogenesis and rapidly develop next-generation therapeutics. As experimental methods are time-consuming and often cumbersome, there is a need to develop efficient computational protocols and adequately utilize them. To address this issue, we present a unique computational protein design protocol that identifies hotspot residues, resistance mutations and signatures of adaptation in a pathogen’s protein against a bound drug. Using the protocol, the binding affinity between the designed mutants and drug is computed quickly, which offers predictions for comparison with biophysical experiments. The applicability and accuracy of the protocol are shown using case studies of a few protein–drug complexes. As a validation, resistance mutations in severe acute respiratory syndrome coronavirus 2 main protease (Mpro) against narlaprevir (an inhibitor of hepatitis C NS3/4A serine protease) are identified. Notably, a detailed methodology and description of the working principles of the protocol are presented. In conclusion, our protocol will assist in providing a first-hand explanation of adaptation, hotspot-residue variations and surveillance of evolving resistance mutations in a pathogenic protein.

100 项与 Narlaprevir 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D09644	Narlaprevir	J05AP	DB14760

研发状态

批准上市

10 条最早获批的记录,

登录

后查看更多信息

适应症	国家/地区	公司	日期
丙型肝炎	俄罗斯	R-Pharm Group	2016-06-03

未上市

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
丙型肝炎	临床3期	美国	Merck GmbH	-
慢性丙型肝炎基因型 1	临床前	-	Merck Sharp & Dohme Corp.	2007-07-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00689390 (CTgov)	临床2/3期	慢性丙型肝炎	1,954	Blood/Plasma Collection+Boceprevir+Peginterferon alfa-2b+ribavirin (Participants From Boceprevir Studies)	(範鬱築簾鹹簾鹹鹹築積) = 壓鹹築餘夢醖獵醖淵繭艱憲觸觸膚觸築觸製構 (鹽齋鹹願蓋鏇憲築蓋獵, 艱鑰顧襯鹽鏇襯憲積淵 ~ 構窪淵蓋構淵鬱窪襯壓) 更多	-	2015-10-06
				Blood/Plasma Collection+Narlaprevir+Peginterferon alfa-2b+ribavirin (Participants From Narlaprevir Studies)	(範鬱築簾鹹簾鹹鹹築積) = 顧範鏇艱築觸繭窪鹽獵艱憲觸觸膚觸築觸製構 (鹽齋鹹願蓋鏇憲築蓋獵, 範齋蓋簾顧觸鑰壓築窪 ~ 鬱繭糧憲鏇夢構夢獵築) 更多
NCT03537404 (CTgov)	临床1期	-	36	Narlaprevir+Tenofovir Disoproxil Fumarate+Ritonavir (Treatment C (Part 1))	簾鹹廠齋願壓襯鹽壓觸(艱築艱鏇願鏇製膚餘鏇) = 選衊壓積襯觸膚簾構壓鹽鏇築選窪齋顧鏇觸繭 (鏇淵醖積選範襯顧選願, 遞簾顧艱顧鬱構齋廠餘 ~ 繭夢廠夢範獵夢積蓋窪) 更多	-	2019-02-19
				Narlaprevir+Ritonavir+raltegravir (Treatment C (Part 2))	簾鹹廠齋願壓襯鹽壓觸(艱築艱鏇願鏇製膚餘鏇) = 遞鑰窪積築糧網憲憲遞鹽鏇築選窪齋顧鏇觸繭 (鏇淵醖積選範襯顧選願, 窪襯齋鬱築簾遞構築網 ~ 鑰糧鹹夢製壓夢壓鏇顧) 更多