更新于：2024-11-01

HBV-X

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 HBV-X 相关的药物

RBD-1016

靶点

HBV-X

作用机制

HBV-X抑制剂

在研机构

Ribocure Pharmaceuticals AB [+1]

原研机构

苏州瑞博生物技术股份有限公司

在研适应症

慢性丁型肝炎 [+3]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 HBV-X 相关的临床试验

CTIS2023-509007-33-00 / Recruiting

A phase 2a, multicentre trial to evaluate the efficacy, safety and pharmacokinetics of RBD1016 in participants with chronic hepatitis D virus infection, including a randomized, single-blinded, placebo-controlled exploratory part - RC04T001

开始日期2024-08-21

申办/合作机构

Ribocure Pharmaceuticals AB

NCT06649266 / Recruiting临床2期

A Phase 2a, Multicentre Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of RBD1016 in Participants With Chronic Hepatitis D Virus Infection, Including a Randomised, Single Blinded, Placebo-controlled Exploratory Part

The goal of this clinical trial is to learn if drug RBD1016 works to treat chronic hepatitis D virus infection in adults. It will also learn about the safety of drug RBD1016. The main questions it aims to answer are:
Does drug RBD106 reduce the HDV RNA levels? What medical problems may participants experience when taking drug RBD1016? Researchers will compare drug RBD1016 to a placebo to see if drug RBD1016 works to treat chronic hepatitis D.
Participants will:
Receive drug RBD1016 or a placebo several times throughout the trial. Visit the clinic once every 4-6 weeks for checkups and tests.

开始日期2024-08-21

申办/合作机构

Ribocure Pharmaceuticals AB

CTIS2023-503880-40-00 / Recruiting

A phase II clinical trial to evaluate the safety, efficacy, and pharmacokinetics of RBD1016 injection in participants with chronic hepatitis B - RBHB1203

开始日期2023-09-19

申办/合作机构

苏州瑞博生物技术股份有限公司

100 项与 HBV-X 相关的临床结果

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100 项与 HBV-X 相关的转化医学

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0 项与 HBV-X 相关的专利（医药）

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166

项与 HBV-X 相关的文献（医药）

2024-06-01·Journal of Hepatology

HIV coinfection exacerbates HBV-induced liver fibrogenesis through a HIF-1α- and TGF-β1-dependent pathway

Article

作者: Xu, Min ; Salloum, Shadi ; Chung, Raymond T ; Yu, Xu ; Warner, Charlotte ; Duan, Xiaoqiong ; Chen, Pei-Jer ; Wang, Yongtao ; Li, Wenting ; Lin, Wenyu ; Shao, Tuo ; Jeyarajan, Andre J ; Cheng, Zhimeng

BACKGROUND & AIMSPersons with chronic HBV infection coinfected with HIV experience accelerated progression of liver fibrosis compared to those with HBV monoinfection. We aimed to determine whether HIV and its proteins promote HBV-induced liver fibrosis in HIV/HBV-coinfected cell culture models through HIF-1α and TGF-β1 signaling.METHODSThe HBV-positive supernatant, purified HBV viral particles, HIV-positive supernatant, or HIV viral particles were directly incubated with cell lines or primary hepatocytes, hepatic stellate cells, and macrophages in mono or 3D spheroid coculture models. Cells were incubated with recombinant cytokines and HIV proteins including gp120. HBV sub-genomic constructs were transfected into NTCP-HepG2 cells. We also evaluated the effects of inhibitor of HIF-1α and HIV gp120 in a HBV carrier mouse model that was generated via hydrodynamic injection of the pAAV/HBV1.2 plasmid into the tail vein of wild-type C57BL/6 mice.RESULTSWe found that HIV and HIV gp120, through engagement with CCR5 and CXCR4 coreceptors, activate AKT and ERK signaling and subsequently upregulate hypoxia-inducible factor-1α (HIF-1α) to increase HBV-induced transforming growth factor-β1 (TGF-β1) and profibrogenic gene expression in hepatocytes and hepatic stellate cells. HIV gp120 exacerbates HBV X protein-mediated HIF-1α expression and liver fibrogenesis, which can be alleviated by inhibiting HIF-1α. Conversely, TGF-β1 upregulates HIF-1α expression and HBV-induced liver fibrogenesis through the SMAD signaling pathway. HIF-1α small-interfering RNA transfection or the HIF-1α inhibitor (acriflavine) blocked HIV-, HBV-, and TGF-β1-induced fibrogenesis.CONCLUSIONSOur findings suggest that HIV coinfection exacerbates HBV-induced liver fibrogenesis through enhancement of the positive feedback between HIF-1α and TGF-β1 via CCR5/CXCR4. HIF-1α represents a novel target for antifibrotic therapeutic development in HBV/HIV coinfection.IMPACT AND IMPLICATIONSHIV coinfection accelerates the progression of liver fibrosis compared to HBV monoinfection, even among patients with successful suppression of viral load, and there is no sufficient treatment for this disease process. In this study, we found that HIV viral particles and specifically HIV gp120 promote HBV-induced hepatic fibrogenesis via enhancement of the positive feedback between HIF-1α and TGF-β1, which can be ameliorated by inhibition of HIF-1α. These findings suggest that targeting the HIF-1α pathway can reduce liver fibrogenesis in patients with HIV and HBV coinfection.

2024-01-01·Virus Research

Gambogic acid inhibits HBx-mediated hepatitis B virus replication by targeting the DTX1-Notch signaling pathway

Article

作者: Ren, Jihua ; Liu, Yuting ; Cheng, Shengtao ; Zhang, Hui ; Wen, Xu ; Li, Dian ; Tan, Ming ; Chen, Peng

BACKGROUND & AIMSCurrent antiviral drugs, including nucleoside analogs and interferon, fail to eliminate the HBV covalently closed circular DNA (cccDNA), which serves as a transcript template in infected hepatocytes. Silencing the HBV X protein, which plays a crucial role in cccDNA transcription, is a promising approach to inhibit HBV replication. Therefore, the identification of novel compounds that can inhibit HBx-mediated cccDNA transcription is critical.METHODSInitially, a compound library consisting of 715 monomers derived from traditional Chinese medicines known for their liver-protecting properties was established. Then, MTT assays were used to determine the cytotoxicity of each compound. The effect of candidates on Flag-HBx expression was examined by real-time PCR and western blotting in Flag-HBx transfected HepG2-NTCP cells. Ultimately, the antiviral effect of gambogic acid (GA) on HBV was observed in HBV-infected HepG2-NTCP cells. Mechanistically, the functional role of DTX1 in GA-induced HBV inhibition was examined using RNA-seq. Finally, the antiviral effect of GA was estimated in vivo.RESULTSGambogic acid (GA), a natural bioactive compound with a myriad of biological activities, markedly reduced Flag-HBx expression. Potent and dose-dependent reductions in extracellular HBV RNAs, HBV DNA, HBsAg, HBeAg and HBc protein were discovered three days after GA treatment in HBV-infected cells, accompanied by the absence of significant cytotoxicity. Furthermore, our research revealed that GA exhibited a dose-dependent inhibition of HBx expression, which is a pleiotropic protein required for HBV infection in vivo. We explored the mechanisms underlying GA-mediated inhibition of HBV and confirmed that this inhibition is accomplished by upregulating the expression of the DTX1 gene and boosting the Notch signaling pathway. Finally, the inhibitory effect of GA on HBV replication was tested in vivo using a mouse model of hepatitis B virus recombinant cccDNA.CONCLUSIONSHerein, we discovered GA, which is a natural bioactive compound that targets HBx to inhibit hepatitis B virus replication by activating the DTX1-Notch signaling pathway.

2023-03-01·Journal of Clinical Laboratory Analysis

JNK/c‐Jun pathway activation is essential for HBx‐induced IL‐35 elevation to promote persistent HBV infection

Article

作者: Zhu, Qiaoyun ; Ni, Qin ; Ye, Bo ; Li, Xuefen ; Dong, Yuejiao ; Zhu, Chunxia

AbstractBackgroundImmunoregulation plays pivotal roles during chronic hepatitis B virus (HBV) infection. Studies have shown that Interleukin (IL)‐35 is an important molecule associated with inadequate immune response against HBV. However, the mechanisms involved in the up‐regulation of IL‐35 expression during persistent HBV infection remain unknown.MethodsIn this study, we constructed a plasmid expressing the HBV X protein (pCMV‐HBx) to evaluate the relationship between HBx and IL‐35. Activation of the JNK/c‐Jun pathway was analyzed and chromatin immunoprecipitation followed by sequencing and luciferase reporter assays were performed to determine whether c‐Jun could regulate IL‐35 transcription.ResultsHBx can significantly activate IL‐35 promoter in both LO2 and HepG2 cells compared to the control plasmid (pCMV‐Tag2) using the dual‐luciferase assay. Whereas other viral proteins, such as S, preS1, the core protein, had no significant effect on IL‐35 expression. Similarly, WB and qRT‐PCR also showed that HBx can significantly promote IL‐35 expression at protein and mRNA levels in the aforementioned cells. The relevant pathway mechanism showed that the expression of JNK and c‐Jun genes was significantly higher in transfected cells carrying pCMV‐HBx than in the pCMV‐Tag2‐transfected and ‐untransfected cells. WB analysis revealed that phosphorylated JNK and c‐Jun were overexpressed after HBx action. Conversely, the addition of the JNK/c‐Jun signaling pathway inhibitor could significantly suppress HBx‐induced IL‐35 expression in a dose‐dependent manner.ConclusionsA novel molecular mechanism of HBV‐induced IL‐35 expression was revealed, which involves JNK/c‐Jun signaling in up‐regulating IL‐35 expression via HBx, resulting in transactivation of the IL‐35 subunit EBI3 and p35 promoter.

项与 HBV-X 相关的新闻（医药）

2024-06-01

·药时代

【新药进展】全球乙肝新药进展(更新至2024年5月，含EASL2024新药进展，独家整理)

编者按：近几月Hepatitis B Foundation网站乙肝新药表单更新迟滞，为帮助大家更准确及时地获取全球乙肝新药最前沿信息，肝霖君查询各大药企官网更新的产品管线信息和相关网络资料以及EASL2024大会摘要中的乙肝新药报道做了系统整理，并汇总了慢乙肝新药与新药联合、新药与现有药物联合治疗的临床研究进展。本期表单更新有：新增处于临床前研究阶段的siRNA药物SA011和SA012。新药联合治疗的探索明显加速，包括新药与新药联合、新药与现有药物的联合。许多新药单药在I期或II期研究中未达到主要疗效目标，企业便积极开始了不同联合治疗方案的探索。这也将是未来乙肝全面临床治愈的必要策略。新药相关联合用药临床研究汇总部分新药进展01 SA011、SA012SA011和SA012分别是苏州时安生物技术有限公司开发的靶向PD-L1基因和HBV-X基因的GalNAc偶联siRNA，目前均处于临床前研究阶段。在hPD-1/PD-L1 AAV-HBV小鼠模型中，SA012 7.5 mg/kg QW，皮下注射8次，1/7的小鼠实现HBsAg清除，4/7的小鼠HBV DNA检测不到，5/7的小鼠HBsAb水平超40 mIU/mL；SA012联用VIR-2218 1 mg/kg Q4W，皮下注射2次，4/8的小鼠实现HBsAg清除；SA012 + VIR-2218 + SA011进一步提高了HBsAg清除率（6/8）及HBV DNA阴转率（8/8）。在14周研究期间，HBsAg清除的小鼠均未出现反弹。02 AB-729 + PegIFNα + NAAB-729是Arbutus Biopharma和齐鲁制药共同开发的siRNA药物。IIa研究AB-729-201的中期数据显示，AB-729 + NA治疗24周后加用PegIFNα继续治疗24周有28%（7/25）的受试者实现HBsAg清除，7例受试者的anti-HBs水平均> 10 IU/L，其中5/7的受试者anti-HBs > 100 IU/L。03 AB-729 + VTP-300siRNA药物AB-729和治疗性疫苗VTP-300均处于临床II期研究阶段。AB-729-202是一项随机双盲IIa期研究，纳入NA经治获病毒学抑制、HBsAg ≥ 100且≤ 5000 IU/mL、ALT ≤ 2 × ULN的慢乙肝患者先接受AB-729 60 mg Q8W，治疗24周，随后受试者随机分配至Group A或Group B，在第26、30周分别接受VTP-300或安慰剂治疗，所有患者维持NA治疗至第48周。截至目前有36例完成30周治疗，25例完成48周治疗。第48周时，Group A（n = 13）分别有92%和42%的患者HBsAg < 100 IU/mL或< 10 IU/mL，Group B（n = 12）分别为73%和33%；第60周时，Group A（n = 7）分别为100%和57%，Group B（n = 7）分别为2%和0%。Group A、Group B分别有11/13（85%）、5/12（42%）的患者在48周时实现NA停药。04 VTP-300 + 低剂量NivolumabVTP-300是Vaccitech开发的一款治疗性疫苗。一项开放标签、随机、IIb期研究纳入HBsAg ≥ 10且< 4000 IU/mL、NA经治≥ 6个月、HBV DNA ≤ 1000 IU/mL的慢乙肝患者给予VTP-300单药或联合低剂量PD-L1抑制剂（Nivolumab）治疗最长至第85天，70例受试者首次用药后第169天数据显示，在基线HBsAg ≤ 200 IU/mL受试者中实现HBsAg降幅≥ 0.5 log、≥ 1 log的比例分别为59%、27%，在基线HBsAg > 200 IU/mL受试者中分别为13%和2%；VTP-300 + 低剂量Nivolumab组和VTP-300单药组分别有2例、1例受试者实现HBV DNA和HBsAg检测不到。05 RG6346 ± RG7854 ± PegIFNαRG6346（Xalnesiran）是Roche和Dicerna共同开发的siRNA药物，RG7854（Ruzotolimod）是Roche开发的一款TLR-7激动剂。II期研究PIRANGA纳入NUC经治获病毒学抑制的慢乙肝患者随机分为Arm 1（RG6346 100 mg + NUC）、2（RG6346 200 mg + NUC）、3（RG6346 200 mg + RG7854 150 mg + NUC）、4（RG6346 200 mg + PegIFNα + NUC）和5（NUC对照组）。Arm 1 - 5在治疗结束时的HBsAg清除率分别为2/30（6.7%）、1/30（3.3%）、6/34（17.6%）、9/30（30.0%）和0/35（0.0%）；治疗结束后48周的HBsAg清除率分别为3/30（10.0%）、0/30（0.0%）、4/34（11.8%）、5/30（16.7%）和1/35（2.9%）。在治疗结束后48周获HBsAg清除的13例患者中，7例实现NUC停药，9例实现HBsAg血清学转换，其中Arm 1 - 5分别为1、0、2、5、1例。所有达到HBsAg清除的患者其基线HBsAg水平均< 1000 IU/mL。封面图来源：pixabay版权声明/免责声明本文为授权转载文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn从1000亿到1580亿，全球「减重药」市场又增重了！十年之后，默沙东30亿美元重返眼科领域！错过了「星起点」宣讲会？问答实录拿走不谢～点击阅读原文，了解更多！

siRNA临床2期疫苗临床结果临床1期