更新于：2024-11-01

NS3 x CTSB

更新于：2024-11-01

基本信息

关联

项与 NS3 x CTSB 相关的药物

VBY-376

靶点

CTSB x NS3

作用机制

CTSB抑制剂 [+1]

在研机构-

原研机构

Virobay, Inc.

在研适应症-

非在研适应症

慢性丙型肝炎 [+2]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 NS3 x CTSB 相关的临床试验

NCT00557583 / Completed临床1期

A Randomized, Double-blinded, Placebo-controlled, Sequential, Single Ascending Dose Evaluation of the Safety and Pharmacokinetics of VBY-376 in Healthy Adults

The study will evaluate the safety and pharmacokinetics of single doses of VBY-376 in healthy subjects.

开始日期2007-11-01

申办/合作机构

Virobay, Inc.

100 项与 NS3 x CTSB 相关的临床结果

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100 项与 NS3 x CTSB 相关的转化医学

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0 项与 NS3 x CTSB 相关的专利（医药）

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项与 NS3 x CTSB 相关的文献（医药）

2020-06-01·The Plant Pathology Journal3区 · 农林科学

Suppression of Rice Stripe Virus Replication in Laodelphax striatellus Using Vector Insect-Derived Double-Stranded RNAs

3区 · 农林科学

ArticleOA

作者: Choi, Jae Young ; Park, Dong Hwan ; Je, Yeon Ho ; Kim, Jun Young ; Wang, Minghui ; Kim, Woo Jin ; Fang, Ying ; Park, Min Gu ; Kim, Hyun Ji

RNA interference (RNAi) has attracted attention as a promising approach to control plant viruses in their insect vectors. In the present study, to suppress replication of the rice stripe virus (RSV) in its vector, Laodelphax striatellus, using RNAi, dsRNAs against L. striatellus genes that are strongly upregulated upon RSV infection were delivered through a rice leaf-mediated method. RNAi-based silencing of peroxiredoxin, cathepsin B, and cytochrome P450 resulted in significant down regulation of the NS3 gene of RSV, achieving a transcriptional reduction greater than 73.6% at a concentration of 100 ng/μl and, possibly compromising viral replication. L. striatellus genes might play crucial roles in the transmission of RSV; transcriptional silencing of these genes could suppress viral replication in L. striatellus. These results suggest effective RNAi-based approaches for controlling RSV and provide insight into RSV-L. striatellus interactions.

2010-11-01·Antimicrobial Agents and Chemotherapy2区 · 医学

Preclinical Characterization of BI 201335, a C-Terminal Carboxylic Acid Inhibitor of the Hepatitis C Virus NS3-NS4A Protease

2区 · 医学

Article

作者: Cordingley, Michael G. ; Kukolj, George ; Lagacé, Lisette ; White, Peter W. ; Llinàs-Brunet, Montse ; Amad, Ma'an ; Bolger, Gordon ; Garneau, Michel ; Thibeault, Diane ; Bethell, Richard C. ; Duan, Jianmin

ABSTRACT BI 201335 is a hepatitis C virus (HCV) NS3-NS4A (NS3 coexpressed with NS4A) protease inhibitor that has been shown to have potent clinical antiviral activity. It is a highly optimized noncovalent competitive inhibitor of full-length NS3-NS4A proteases of HCV genotypes 1a and 1b with K i values of 2.6 and 2.0 nM, respectively. K i values of 2 to 230 nM were measured against the NS3-NS4A proteases of HCV genotypes 2 to 6, whereas it was a very weak inhibitor of cathepsin B and showed no measurable inhibition of human leukocyte elastase. BI 201335 was also shown to be a potent inhibitor of HCV RNA replication in vitro with 50% effective concentrations (EC 50 s) of 6.5 and 3.1 nM obtained in genotype 1a and 1b replicon assays. Combinations of BI 201335 with either interferon or ribavirin had additive effects in replicon assays. BI 201335 had good permeability in Caco-2 cell assays and high metabolic stability after incubation with human, rat, monkey, and dog liver microsomes. Its good absorption, distribution, metabolism, and excretion (ADME) profile in vitro , as well as in rat, monkey, and dog, predicted good pharmacokinetics (PK) in humans. Furthermore, drug levels were significantly higher in rat liver than in plasma, suggesting that distribution to the target organ may be especially favorable. BI 201335 is a highly potent and selective NS3-NS4A protease inhibitor with good in vitro and animal ADME properties, consistent with its good human PK profile, and shows great promise as a treatment for HCV infection.

2004-04-01·Biochimica et Biophysica Acta (BBA) - General Subjects

Structure–activity relationships for the selectivity of hepatitis C virus NS3 protease inhibitors

Article

作者: Eva Åkerblom ; Bertil Samuelsson ; Anders Hallberg ; U.Helena Danielson ; Anja Johansson ; Anton Poliakov ; Karin Oscarsson

The selectivity of hepatitis C virus (HCV) non-structural protein 3 (NS3) protease inhibitors was determined by evaluating their inhibitory effect on other serine proteases (human leukocyte elastase (HLE), porcine pancreatic elastase (PPE), bovine pancreatic chymotrypsin (BPC)) and a cysteine protease (cathepsin B). For these peptide inhibitors, the P1-side chain and the C-terminal group were the major determinants of selectivity. Inhibitors with electrophilic C-terminal residues were generally non-selective while compounds with non-electrophilic C-terminal residues were more selective. Furthermore, compounds with P1 aminobutyric acid residues were non-selective, while 1-aminocyclopropane-1-carboxylic acid (ACPC) and norvaline-based inhibitors were generally selective. The most potent and selective inhibitors of NS3 protease tested contained a non-electrophilic phenyl acyl sulfonamide C-terminal residue. HLE was most likely to be inhibited by the HCV protease inhibitors, in agreement with similar substrate specificities for these enzymes. The identified structure-activity relationships for selectivity are of significance for design of selective HCV NS3 protease inhibitors.