A Phase II, Multi-centre Open Label Study to Assess the Efficacy and Safety of Oral Apabetalone With Background Dapagliflozin in Subjects With Long -COVID-19 (Post-COVID-19 Conditions) and Type 2 Diabetes Mellitus (T2DM)

This is an open label, multicentre, phase II clinical trial that aims to assess the efficacy and safety of oral Apabetalone with background dapagliflozin for up to 12 weeks in T2DM patients with a history of probable or confirmed SARS-CoV-2 infection, with symptoms within 3 months from the onset of COVID-19 that last for at least 2 months and cannot be explained by an alternative diagnosis.

开始日期2025-04-15

申办/合作机构

Resverlogix Corp.

NCT03160430

/ Not yet recruiting临床1/2期

A Two-Part Phase 2a Study in Patients With End-Stage Renal Disease Treated With Hemodialysis; Part A is an Open-Label Study Arm to Evaluate the Effect of Hemodialysis on the Pharmacokinetics of 100 mg RVX000222; and Part B is a Double-Blind, Randomized, Placebo-Controlled, Sequential Cross-Over Study Arm to Evaluate the Efficacy, Safety, and Pharmacokinetics of RVX000222

This is a multi-center, two-part study; Part A and Part B. Part A of the study is an open-label, single-dose pharmacokinetic (PK) evaluation of 100 mg RVX000222 on dialysis and non-dialysis days in eight (8) End Stage Renal Disease (ESRD) patients who receive hemodialysis as standard of care.
Part B of the study is a double-blind, placebo-controlled study in up to thirty six (36) ESRD patients receiving hemodialysis using a sequential cross-over design with RVX000222 at a daily oral dose of 100 mg b.i.d. (200 mg per day) or matching placebo in combination with SoC.
The primary objective of the study is to evaluate if treatment with RVX000222 in combination with standard of care (SoC) decreases plasma alkaline phosphatase in comparison to placebo and SoC.

开始日期2024-11-22

申办/合作机构

Resverlogix Corp.

NCT04915300

/ Unknown status临床2期IIT

Apabetalone for Pulmonary Arterial Hypertension: a Phase 2 Clinical Study

Throughout the past twenty years, numerous specific pharmacologic agents targeting the endothelial dysfunction associated with PAH have emerged. Short term placebo-controlled randomized trials assessing PAH-specific monotherapy with these molecules have reported improvements in pulmonary hemodynamics and exercise capacity. A recent meta-analysis also documented a reduction in short-term mortality of about ≈40% with such therapies. Several randomized clinical trials evaluating PAH-specific combination therapy have been conducted. Our recent meta-analysis showed that combination therapy was associated with a 35% risk reduction for the occurrence of clinical worsening compared to monotherapy. Nonetheless, the investigators also showed 17% of PAH patients receiving combination therapy still experienced clinical worsening over a median exposure of 16 weeks. Moreover, long-term survival on PAH-specific also therapy remains poor in the modern era, with a yearly mortality rate of 15 % in incident idiopathic PAH. The identification of innovative therapeutic targets and validation of these complementary therapeutic interventions are thus urgently needed in PAH.
The investigators and others (K. Stenmark, University of Colorado and H. Bogaard, VU University Medical Center, Amsterdam, personal communications), have published strong evidence that BRD4 plays a key role in the pathological phenotype in PAH accounting for disease progression and showed that BRD4 inhibition can reverse PAH in several animal models. Intriguingly, coronary artery disease (CAD) and metabolic syndrome are more prevalent in PAH compared with the global population, suggesting a link between these diseases. Interestingly, BRD4 is also a trigger for calcification and remodeling processes and regulates transcription of lipoprotein and inflammatory factors, all of which are important in PAH and CAD. Apabetalone, an orally available BRD4 inhibitor, is now in a clinical development stage with a good safety profile.
The overall objective of the study is to explore the efficacy and safety of apabetalone as an add-on therapy for adult PAH patients and to inform the conduct and the design of a Phase 3 trial.
The primary objective of the study is to assess the efficacy of apabetalone as evaluated by the change in PVR over a period of 24 weeks compared to placebo in adult subjects with PAH on stable background therapy.
Secondary objectives include changes at week 24 in 6MWD, plasma NT-proBNP concentration, WHO functional class, ESC/ERS risk stratification score, health-related quality of life and additional hemodynamic data from right heart.
Exploratory objectives are to evaluate the effects of apabetalone compared to placebo in adult subjects with PAH on mortality and clinically relevant morbidity events, and on circulating levels and transcription changes in whole blood markers of metabolism, vascular calcification, inflammation, DNA damage and leucocyte expression of BMPR2.

开始日期2023-10-01

申办/合作机构

Université Laval

[+2]

100 项与 Apabetalone 相关的临床结果

登录后查看更多信息

100 项与 Apabetalone 相关的转化医学

登录后查看更多信息

100 项与 Apabetalone 相关的专利（医药）

登录后查看更多信息

100

项与 Apabetalone 相关的文献（医药）

2026-02-01·Advanced Science

Brd4 BD1 Domain Antagonism of MS436 Preserves Blood‐Brain Barrier Integrity via Rnf43/β‐Catenin Signaling Pathway

Article

作者: Yong Zhang ; Yushan Du ; Fen Ji ; Xiaochen Zhang ; Jingjing Zhang ; Chenxiao Li ; Jiangwei Xia ; Jianwei Jiao ; Shuang Liu ; Sihan Li ; Shukui Zhang

Abstract:

Blood‐brain barrier (BBB) disruption is central to neurodegenerative and cerebrovascular diseases, but its causal role and therapeutic targeting remain challenging. Bromodomain and extraterminal domain (BET) proteins, particularly Brd4, regulate transcription via dual bromodomains (BD1, BD2). While BD1 antagonists are explored for tumors and BD2 antagonists for inflammation, their impact on cerebrovascular integrity is unclear. Crucially, opposing BBB effects of domain‐specific BET antagonism: the BD2 antagonist RVX208 disrupt the BBB, whereas the BD1 antagonist MS436 significantly reduces leakage and improves neurological outcomes, revealing therapeutic potential is demonstrated. Mechanistically, endothelial Brd4 critically suppresses BBB stability. Its ablation upregulates tight junction (TJ) proteins. Brd4, acting exclusively through its BD1 domain, destabilizes TJs via Rnf43 is identified, which promotes β‐catenin and TJ protein degradation. This defines a novel Brd4 BD1/Rnf43/β‐catenin axis essential for BBB integrity. The findings establish Brd4 BD1 inhibition as a novel BBB‐protective strategy and position MS436 for repurposing in cerebrovascular diseases, necessitating reevaluation of domain‐specific BET targeting for neurovascular pathologies.

2025-12-01·DRUG DISCOVERY TODAY

Inhibition of bromodomain and extra-terminal motif (BET) proteins in pediatric sarcoma: A systematic review of in vitro and in vivo studies

Review

作者: Lambona, Chiara ; Rota, Rossella ; Marchese, Cinzia ; Locatelli, Franco ; Zwergel, Clemens ; Cassandri, Matteo ; Macrì, Elisa ; Pomella, Silvia ; Barillari, Giovanni ; Ferraro, Erika

BET inhibitors (BETi), especially those targeting BRD4, show promising preclinical activity against pediatric sarcomas by disrupting oncogenic transcription. This systematic review of 26 studies highlights the anti-proliferative and pro-apoptotic effects of BETi across five pediatric sarcoma types. In vivo data show a decrease in tumor growth, with better results when combined with other therapies. This systematic review revealed that, whereas early investigations mostly rely on pan-BETi, recent studies focus on newer and more specific agents. Accordingly, we reported that ABBV-744 and RVX-208, which selectively target the BD2 domain, and GNE-987, a specific BRD4 degrader, are the most promising inhibitors. However, ABBV-075, a pan-BETi, also exhibits high efficacy, being effective at low doses. Nevertheless, translating these experimental findings into clinical practice remains difficult because of resistance, toxicity, and inconsistent responses. Future approaches include using biomarkers for patient selection, developing isoform-specific BETi, and designing rational combination therapies to enhance treatment for these aggressive pediatric cancers.

2025-05-01·Kidney International Reports

Corrigendum to “The Bromodomain and Extraterminal Protein Inhibitor Apabetalone Ameliorates Kidney Injury in Diabetes by Regulating Cholesterol Accumulation and Modulating the Gut Microbiota” [Volume 10, Issue 2, February 2025, Pages 522-534]

作者: Qiuling Fan ; Xin Li ; Min Wang ; He Sun ; Zhaohui Huang ; Yonghong Zhu

[This corrects the article DOI: 10.1016/j.ekir.2024.11.022.].

项与 Apabetalone 相关的新闻（医药）

2026-02-18

·resverlogix.com

Resverlogix Closes $2.8 Million Shares-for-Interest Private Placement

CALGARY, Alberta, February 18, 2026, Resverlogix Corp. (“Resverlogix”) (TSX:RVX) announced today that it has closed a $2.8 million shares-for-interest private placement with an immediate family member (the “Subscriber”) of Resverlogix’s Chairman and CEO. Under the terms of the shares-for-interest transaction, the Subscriber subscribed for 28,000,000 common shares at CAD$0.10 per share for aggregate proceeds of CAD$2.8 million. After giving effect to the transaction, the Subscriber holds approximately 9.7% of Resverlogix's common shares. The common shares are subject to a four-month hold period. The shares-for-interest transaction followed the settlement of CAD$2.8 million of accrued interest on indebtedness owing to the Subscriber by Zenith Capital Corp. (“Zenith”) by way of the assignment to the Subscriber of an equal amount of accrued interest on indebtedness owing by Resverlogix to Zenith Capital Corp. The securities described herein have not been, and will not be, registered under the United States Securities Act of 1933, as amended (the "U.S. Securities Act"), or any state securities laws, and accordingly, may not be offered or sold to, or for the account or benefit of, persons in the United States or to U.S. Persons (as such term is defined in Regulation S under the U.S. Securities Act), except in compliance with the registration requirements of the U.S. Securities Act and applicable state securities requirements or pursuant to exemptions therefrom. This press release does not constitute an offer to sell or a solicitation of an offer to buy any of Resverlogix's securities to, or for the account or benefit of, persons in the United States or U.S. Persons. Founded in 2001, Resverlogix is a Calgary based late-stage biotechnology company, and a world leader in epigenetics, with the goal of developing first-in-class therapies for the benefit of patients with chronic disease. Resverlogix is developing a new class of epigenetic therapies designed to regulate the expression of disease-causing genes. We aim to improve patients’ lives by restoring biological functions – altered by serious illnesses such as cardiovascular disease – back to a healthier state. The Company’s clinical program is focused on evaluating the lead epigenetic candidate apabetalone for the treatment of cardiovascular disease, associated comorbidities, and post COVID-19 conditions. Resverlogix common shares trade on the Toronto Stock Exchange (TSX:RVX). Follow us on: X.com: @Resverlogix_RVX LinkedIn: https://www.linkedin.com/company/resverlogix-corp-/ This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts”, and other similar expressions. In particular, this news release includes forward looking information related to the potential role of apabetalone in the treatment of patients with cardiovascular disease, post COVID-19 conditions, pulmonary arterial hypertension, associated comorbidities, and other chronic diseases. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our Annual Information Form and most recent MD&A which are incorporated herein by reference and are available through SEDAR at www.sedar.com. The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. The Company disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. For further information please contact: Investor Relations Email: ir@resverlogix.com Phone: 403-254-9252 www.resverlogix.com

2026-01-22

·生物力学仪器

STTT 肾纤维化：从机制到治疗药物

一、背景与概述 CKD 全球负担：影响约10–14%的全球人口，是导致终末期肾病的主要原因。肾脏纤维化是CKD的共同病理特征，表现为细胞外基质（ECM）过度沉积、肾小管萎缩、间质炎症、肾小球硬化和血管稀少。目前尚无特异性的抗纤维化药物，临床治疗主要依赖RAS阻断剂、SGLT2抑制剂等延缓疾病进展。二、肾脏纤维化的关键机制1. 纤维化微环境由受损的实质细胞（如肾小管上皮细胞）与非实质细胞（免疫细胞、间充质细胞）在纤维化区域相互作用形成。2. 肌成纤维细胞的来源与激活主要来源包括：间质成纤维细胞周细胞 Gli1+ MSC样细胞其他（内皮细胞、循环骨髓来源细胞等）激活机制涉及TGF-β、Wnt、Notch等多种信号通路。图 1：肌成纤维细胞的起源和激活 3. 肾小管与间质对话损伤的肾小管通过分泌TGF-β、Wnt、Hedgehog等因子，激活肌成纤维细胞并促进ECM沉积。肾小管细胞周期阻滞和衰老（SASP表型）也是推动纤维化的重要因素。4. 免疫细胞的作用巨噬细胞、T细胞、中性粒细胞、嗜碱性粒细胞等均参与炎症反应和纤维化进程。特别是M2型巨噬细胞、Th17细胞和中性粒细胞在纤维化微环境中起关键作用。5. ECM网络重构基质细胞蛋白（如Tenascin-C）在纤维化肾中显著升高，通过整合素/FAK/MAPK信号促进纤维化。三、表观遗传学在肾脏纤维化中的作用 DNA甲基化：某些基因（如RASAL1、KLOTHO）的高甲基化与纤维化相关。组蛋白修饰：组蛋白乙酰化（HATs/HDACs调控）影响染色质开放性与基因表达。组蛋白甲基化（如H3K9me、H3K27me）参与纤维化相关基因的沉默或激活。非编码RNA： miRNA（如miR-21、miR-29）在纤维化中发挥促进或抑制作用。 lncRNA 通过调控染色质结构和基因转录参与纤维化进程。图2：肾纤维化中的组蛋白修饰和DNA甲基化四、生物标志物尿液标志物：KIM-1、MMP-7、Tenascin-C、DKK3、miR-196a等血液标志物：Galectin-3、sCD163、suPAR、CCL5、VCAM-1等这些标志物有望用于无创评估纤维化程度和疾病进展。图3：尿液和血液中的非侵入性肾纤维化生物标志物五、治疗策略与药物开发现有临床药物（非特异性抗纤维化）： RAS阻断剂、SGLT2抑制剂、GLP-1受体激动剂等可延缓CKD进展。正在研究的抗纤维化药物： Pirfenidone（吡非尼酮）：抑制TGF-β，临床试验中显示对DKD和FSGS患者有一定疗效。 FG-3019（抗CTGF抗体）：初步临床显示耐受良好，可减少微量白蛋白尿。 Bardoxolone methyl（Nrf2激活剂）：可提高eGFR，但心血管风险需关注。 Apabetalone（BET蛋白抑制剂）：在CKD患者中显示对eGFR的积极影响。其他：抗miR-21药物RG-012、Galectin-3拮抗剂GCS-100等。新兴治疗方向：靶向衰老细胞（senolytic therapy）表观遗传药物（如HDAC抑制剂、BET抑制剂）靶向递送系统（如细胞外囊泡、纳米药物）六、挑战与展望早期诊断困难：缺乏敏感、特异的非侵入性生物标志物。治疗时机晚：纤维化常在中晚期才被诊断。药物研发障碍：靶向单一通路可能不足以逆转纤维化，需多靶点联合治疗。传统中药潜力：部分中药成分（如雷公藤红素、淫羊藿苷）在实验模型中显示抗纤维化作用，但临床证据有限。总结肾脏纤维化是CKD进展的核心环节，涉及复杂的细胞间对话、表观遗传调控和免疫炎症反应。尽管目前尚无特效抗纤维化药物，但随着单细胞技术、表观遗传学和靶向递送系统的发展，未来有望实现更精准的诊断与治疗。 “阅读原文”可查看原文献https://doi.org/10.1038/s41392-023-01379-7 提供细胞机械刺激培养系统：包括细胞牵张拉伸、压缩、剪切、电刺激仪器；向有意向客户提供试用30天服务。提供Piuma系列生物纳米压痕仪：可测量细胞、组织、软骨、水凝胶、类器官、高分子材料等生物软物质力学性能参数：杨氏模量（5pa~1Gpa）、粘弹性（松弛、蠕变、储能、损耗）等，向有意向客户提供试样服务。提供生物材料微小力学测试仪器：可测量细胞球、水凝胶球、鱼卵、蛛丝、微针、巩膜、角膜、基质透镜、瓣膜、血管、组织工程支架、肌腱、皮肤、薄膜等生物材料的拉伸、压缩、弯曲、剪切等力学性能。向有意向客户提供试样服务。欢迎咨询交流（扫描二维码可添加微信，也可直接拨打 153-3688-1895）

2025-12-11

·国际糖尿病idiabetes

新型降脂策略综述盘点：RNA类、小分子类及蛋白类疗法

点击“蓝字”关注我们血脂异常仍是动脉粥样硬化性心血管疾病（ASCVD）的核心可改变危险因素。尽他汀类药物、依折麦布、贝特类药物及ω-3脂肪酸已在降脂治疗中确立重要地位，但许多患者仍因低密度脂蛋白胆固醇（LDL-C）降幅不足、富含甘油三酯（TG）脂蛋白升高、遗传性脂蛋白（a）[Lp(a)]升高等原因，存在显著的残余风险。近年来，降脂治疗手段取得了突破性进展，包括新一代小分子药物、单克隆抗体、蛋白类输注制剂及核糖核酸（RNA）类策略等。临床结局试验已证实苯扎贝特、PCSK9抑制剂及二十碳五烯酸乙酯（IPE）的疗效，而针对口服PCSK9抑制剂、靶向Lp(a)的寡核苷酸及ANGPTL3靶向RNA疗法的大规模研究仍在进行中。近日，Endocrinol Metab刊登的一篇综述文章[1]，详细介绍了创新降脂疗法的作用机制、关键临床试验及临床意义，探讨了这些疗法如何重塑未来ASCVD预防的治疗流程。本文撷取精华，整理如下。创新降脂疗法在脂质代谢通路中的作用靶点及干预机制示意图[1] 经典小分子疗法小分子降脂药仍是血脂异常管理和ASCVD预防的核心手段。自20世纪90年代他汀类药物问世（降脂治疗的基石）以来，依折麦布、贝特类药物、苯扎贝特、胆固醇酯转移蛋白（CETP）抑制剂、口服PCSK9抑制剂及Lp(a)抑制剂等新型药物相继研发成功。与单克隆抗体（mAbs）和反义寡核苷酸（ASOs）相比，小分子抑制剂为降低LDL-C和TG提供了口服便捷、成本效益高且作用机制多样的治疗选择。他汀类药物他汀类药物通过抑制限速酶羟甲基戊二酰辅酶A（HMG-CoA）还原酶，减少肝脏胆固醇合成并上调低密度脂蛋白（LDL）受体表达。该类药物彻底革新了降脂治疗，至今仍是降脂治疗的基石，其可使主要不良心血管事件（MACE）发生率降低20%~40%；疗效呈剂量依赖性，高强度他汀类药物可使LDL-C较基线降低超过50%[2-5]。尽管成效显著，但仍有相当比例的患者因他汀类药物不耐受、LDL-C降幅不足、TG升高或Lp(a)升高等因素，心血管疾病风险仍处于高水平。这一治疗缺口推动了具有互补作用机制的新型小分子降脂疗法的研发。依折麦布依折麦布可阻断肠道胆固醇吸收。指南推荐：对于ASCVD患者，若最大耐受剂量他汀类药物治疗后LDL-C仍未达标，依折麦布为首选非他汀类辅助治疗药物；对于他汀类药物不耐受患者，依折麦布可作为单药治疗或与其他药物联合治疗的合理选择。欧洲指南支持早期联合使用他汀类药物与依折麦布，以更可靠地达到基于风险的LDL-C目标值。贝特类药物贝特类药物通过激活过氧化物酶体增殖物激活受体α（PPARα）发挥调脂作用，可降低血浆TG水平并轻度升高高密度脂蛋白胆固醇（HDL-C）。近年来，研究焦点转向新一代选择性PPARα调节剂（SPPARMα），如佩玛贝特（Pemafibrate）。与传统贝特类药物相比，佩玛贝特经设计具有更优的疗效和安全性，可强效降低TG（45%~50%）并升高HDL-C，且肾毒性和肝毒性发生率更低。然而，大规模临床试验PROMINENT结果显示，佩玛贝特虽使TG显著降低（约26%），但未改善心血管结局[6]。这一结果凸显了贝特类药物研究中的一个常见主题：在广泛人群中，强效的TG降低并不一定转化为ASCVD事件减少。尽管如此，贝特类药物在重度高甘油三酯血症的治疗中仍发挥重要临床作用，其即时治疗目标是预防急性胰腺炎而非减少ASCVD事件。烟酸烟酸可降低肝脏极低密度脂蛋白（VLDL）生成并升高HDL-C，但有试验显示[7,8]，在他汀类药物治疗基础上加用烟酸无额外获益，且不良反应发生率增加。因此，烟酸目前已极少使用。 ω-3脂肪酸二十碳五烯酸（EPA）是唯一被证实具有心血管保护获益的ω-3脂肪酸。REDUCE-IT试验（IPE干预降低心血管事件试验）显示，接受他汀类药物治疗的TG升高患者，每日服用4克纯化EPA可使主要心血管事件减少25%，其获益超出单纯TG降低的预期[9]。亚组研究提示，抗炎、抗血栓和斑块稳定机制可能参与其中。相比之下，其他ω-3脂肪酸制剂的疗效呈中性。因此，当前指南推荐：对于接受他汀类药物治疗后仍存在持续性高甘油三酯血症的患者，可使用高剂量纯化EPA；而EPA/DHA复合制剂或低剂量鱼油不建议用于ASCVD预防。新型小分子疗法 Bempedoic Acid Bempedoic Acid是一种肝脏激活型三磷酸腺苷-柠檬酸裂解酶（ACLY）抑制剂，单药治疗可使低密度脂蛋白胆固醇（LDL-C）降低约18%，与依折麦布组成复方制剂联合使用时降幅可达30%~35%[10]。现行欧洲指南已将Bempedoic Acid纳入阶梯式LDL-C降低治疗流程，推荐用于无法使用他汀类药物、或经最大耐受剂量他汀类药物（联合或不联合依折麦布）治疗后LDL-C仍未达标的患者。胆固醇酯转移蛋白（CETP）抑制剂 CETP抑制剂通过减少胆固醇酯从高密度脂蛋白（HDL）向载脂蛋白B（ApoB）含载脂蛋白的转移，同时升高HDL-C并降低LDL-C。尽管作用机制具有充分的理论依据，但第一代CETP抑制剂的临床结果令人失望。这些失败使CETP作为可行治疗靶点的合理性受到质疑。目前，新一代CETP抑制剂Obicetrapib重新点燃了该通路的研究热情。若试验成功，Obicetrapib可能重新确立CETP抑制疗法的临床价值，成为高危患者通过全口服方案实现强效LDL-C达标目标的重要手段。口服PCSK9抑制剂口服PCSK9抑制剂（如AZD0780）是一项重要进展。口服PCSK9抑制剂试验（AZD0780）（PURSUIT）Ⅱb期结果显示，治疗12周时，该药物可呈剂量依赖性降低LDL-C约50%，且耐受性良好[11]。若Ⅲ期临床试验证实其在降低心血管结局事件方面与mAbs相当，口服PCSK9抑制剂可能会扩大治疗的可及性，惠及更广泛的患者群体。脂蛋白（a）[Lp(a)]抑制剂 Muvalaplin是一种口服小分子药物，用于高Lp(a)患者的Ⅱ期临床试验（KRAKEN）显示，其可使Lp(a)降低高达86%，同时次要终点apoB和LDL-C也有所降低。鉴于Lp(a)升高是心血管疾病的独立危险因素，Muvalaplin有望填补这一重大未被满足的临床需求。 BET抑制剂 Apabetalone是一种溴结构域和超末端结构域（BET）蛋白抑制剂，可增加载脂蛋白A-I（apoA-I）表达并升高HDL-C。尽管该药用于2型糖尿病合并近期急性冠脉综合征（ACS）患者主要不良心血管事件的试验（BETonMACE）未达到主要终点，但心力衰竭住院率的降低提示，其可能对同时存在ASCVD和心力衰竭风险的患者具有选择性治疗价值。 MTP抑制剂 Lomitapide抑制微粒体甘油三酯转移蛋白（MTP），阻止ApoB含载脂蛋白的组装。该药物获批用于纯合子家族性高胆固醇血症（HoFH）的治疗，可独立于LDL受体活性降低LDL-C达50%，但胃肠道不耐受和肝脂肪变性限制了其临床应用。单克隆抗体与蛋白类疗法 PCSK9单克隆抗体的研发、机制与临床试验 PCSK9可与肝细胞表面的低密度脂蛋白受体（LDL-R）结合，促进受体的溶酶体降解，从而降低肝脏对循环中LDL-C的清除能力。依洛尤单抗（Evolocumab）、阿利西尤单抗（Alirocumab）等靶向PCSK9的抑制性单克隆抗体，可阻断这一相互作用，促进LDL受体再循环，增强肝细胞对LDL-C的摄取，最终显著降低血浆LDL-C水平[12]。血管生成素样蛋白 3（ANGPTL3）抑制与残余胆固醇降低 ANGPTL3是一种源于肝脏的脂蛋白脂肪酶（LPL）和内皮脂肪酶抑制剂，调控TG和残余胆固醇代谢。携带ANGPTL3功能缺失突变的个体，LDL-C、TG及残余胆固醇水平显著降低，冠心病风险也随之下降[13]。 ANGPTL3抑制和调控甘油三酯代谢的机制[1] Evinacumab是一款靶向ANGPTL3的全人源单克隆抗体，已获美国食品药品监督管理局（FDA）批准用于纯合子HoFH治疗，尽管疗效显著，但目前仅获批孤儿药适应证，且需静脉注射，这限制了其广泛应用。在二级预防场景中开展大规模临床试验的可行性仍不明确，不过基于小干扰RNA（siRNA）的ANGPTL3抑制疗法的研发，为未来提供了颇具前景的治疗选择。 RNA类疗法 RNA类降脂药物主要采用两种分子策略：反义寡核苷酸和小干扰RNA。这两种技术平台均利用内源性通路降低脂质代谢相关靶蛋白的表达，但在分子设计、作用机制和效应持续时间上存在差异。靶向PCSK9的RNA疗法 PCSK9是LDL-R稳态的关键调控因子，可促进LDL-R的溶酶体降解，从而升高循环中LDL-C水平。英克司兰（inclisiran）是一种GalNAc偶联siRNA，靶向肝细胞内的PCSK9 mRNA。Ⅲ期ORION-9、ORION-10和ORION-11试验显示，在最大耐受剂量他汀类药物治疗基础上，英克司兰于给药第0天、第3个月及之后每6个月给药一次，可持续降低LDL-C约50%[14]。ORION-3试验的长期延长期数据表明，其疗效和安全性可维持4年[15]。靶向Lp(a)的RNA疗法 Lp(a)是一种与载脂蛋白（a）共价结合的类LDL颗粒，载脂蛋白（a）是一种结构与纤溶酶原相似的糖蛋白。Lp(a)升高是ASCVD的因果性独立危险因素。传统降脂药物对Lp(a)水平影响甚微，因此亟需靶向疗法。 Pelacarsen是一种GalNAc偶联ASO，靶向LPA基因mRNA。Ⅱ期研究显示，对于确诊ASCVD且Lp(a)升高的患者，每月给药一次可使Lp(a)水平降低达80%[16]。lepodisiran是一种在研的超长效GalNAc偶联siRNA，靶向LPA基因mRNA，设计给药频率极低（可能为每年一次）。Ⅱ期ALPACA试验显示，采取单次皮下注射，第60天时Lp(a)降低93.9%，且降幅＞80%的效果可维持近1年[17]。Zerlasiran是另一种siRNA，可抑制肝脏载脂蛋白（a）的产生，从而显著降低Lp(a)水平。靶向载脂蛋白C-Ⅲ（ApoC-Ⅲ）的RNA疗法 ApoC-Ⅲ是TG代谢的关键调控因子，可抑制脂蛋白脂肪酶活性，延缓甘油三酯- rich脂蛋白（TRLs）的清除。Volanesorsen是第二代ASO，在家族性乳糜微粒血症综合征（FCS）和多因素重度高甘油三酯血症患者中显示出显著的TG降低效果。然而，其使用受到血小板减少症和注射部位反应的限制，未获FDA批准。靶向ApoC-Ⅲ疗法的另一重要进展是Olezarsen，这是一种GalNAc偶联ASO，可直接降低肝细胞内APOC3基因mRNA水平。通过沉默ApoC-Ⅲ的产生，Olezarsen可降低TG水平，改善残余脂蛋白清除，并有利调节动脉粥样硬化性脂蛋白代谢。另一款靶向ApoC-Ⅲ的疗法Plozasiran，作为新一代siRNA，旨在沉默肝脏APOC3基因表达。Ⅱ期SHASTA-2试验（评估ARO-APOC3在重度高甘油三酯血症成人患者中的疗效）显示，重度高甘油三酯血症患者接受Plozasiran治疗后，TG显著降低近60%，ApoC-Ⅲ水平下降超过80%[18]。MUIR试验中，Plozasiran在24周时显著降低混合性高脂血症患者的TG水平[19]。靶向ANGPTL3和载脂蛋白B-100（ApoB-100）的RNA疗法 ANGPTL3可抑制脂蛋白脂肪酶和内皮脂肪酶活性。Zodasiran是一种GalNAc偶联siRNA，靶向肝细胞内的ANGPTL3 mRNA。通过沉默ANGPTL3，可同时降低TG、LDL-C、非HDL-C、ApoB和残余胆固醇，解决残余脂质风险的多个组分。 ApoB-100是动脉粥样硬化性脂蛋白组装和分泌的关键分子。Mipomersen是靶向ApoB mRNA的第二代ASO，可使HoFH患者的LDL-C降低25%[20]。然而，Mipomersen存在多种不良反应，尽管FDA于2013年批准其用于HoFH治疗，但2019年因安全性问题撤销了该批准。结论脂质管理已迈向作用机制多样、精准化的治疗时代。苯扎贝特和IPE已证实具有结局获益，PCSK9单克隆抗体则牢固确立了强效降低LDL-C的临床价值。新一代药物（包括口服PCSK9抑制剂、靶向Lp(a)的寡核苷酸、ANGPTL3抑制剂和靶向ApoC-Ⅲ的RNA疗法）有望解决高危和极高危人群的残余风险。尽管前景广阔，但这些药物在成本、可及性和长期安全性方面仍面临挑战。其临床应用需与指南推荐的治疗流程密切结合，并考虑患者个体风险特征。参考文献（上下滑动可查看） [1]Youngwoo Jang, Eun-Jung Rhee, Sung Hee Choi. Innovative Lipid-Lowering Strategies: RNA-Based, Small Molecule, and Protein-Based Therapies. Endocrinol Metab (Seoul).2025 Oct 29;40(5):668-686. [2]Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet. 1994;344:1383-9. [3]Heart Protection Study Collaborative Group MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22. [4]LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425-35. [5]Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195-207. [6]Das Pradhan A, Glynn RJ, Fruchart JC, MacFadyen JG, Zaharris ES, Everett BM, et al. Triglyceride lowering with pemafibrate to reduce cardiovascular risk. N Engl J Med. 2022;387:1923-34. [7]Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255-67. [8]Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371:203-12.[9]Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.[10]Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023;388:1353-64. [11]Koren MJ, Vega RB, Agrawal N, Xu Y, Barbour AM, Yu H, et al. An oral PCSK9 inhibitor for treatment of hypercholesterolemia: the PURSUIT randomized trial. J Am Coll Cardiol. 2025;85:1996–2007. [12]Lambert G, Sjouke B, Choque B, Kastelein JJ, Hovingh GK. The PCSK9 decade. J Lipid Res. 2012;53:2515-24. [13]Dewey FE, Gusarova V, Dunbar RL, O’Dushlaine C, Schurmann C, Gottesman O, et al. Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease. N Engl J Med. 2017;377:211-21.[14]Ray KK, Raal FJ, Kallend DG, Jaros MJ, Koenig W, Leiter LA, et al. Inclisiran and cardiovascular events: a patient-level analysis of phase III trials. Eur Heart J. 2023;44:129-38. [15]Ray KK, Troquay RP, Visseren FL, Leiter LA, Scott Wright R, Vikarunnessa S, et al. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. Lancet Diabetes Endocrinol. 2023;11:109-19. [16]Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, Tardif JC, Baum SJ, Steinhagen-Thiessen E, et al. Lipoprotein(a) reduction in persons with cardiovascular disease. N Engl J Med. 2020;382:244–55.[17]Nissen SE, Ni W, Shen X, Wang Q, Navar AM, Nicholls SJ, et al. Lepodisiran: a long-duration small interfering RNA targeting lipoprotein(a) N Engl J Med. 2025;392:1673-83. [18]Gaudet D, Pall D, Watts GF, Nicholls SJ, Rosenson RS, Modesto K, et al. Plozasiran (ARO-APOC3) for severe hypertriglyceridemia: the SHASTA-2 randomized clinical trial. JAMA Cardiol. 2024;9:620-30.[19]Ballantyne CM, Vasas S, Azizad M, Clifton P, Rosenson RS, Chang T, et al. Plozasiran, an RNA interference agent targeting APOC3, for mixed hyperlipidemia. N Engl J Med. 2024;391:899-912. [20]Parham JS, Goldberg AC. Mipomersen and its use in familial hypercholesterolemia. Expert Opin Pharmacother. 2019;20:127-31. 声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！（来源：《国际循环》编辑部）

100 项与 Apabetalone 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D11131	Apabetalone	-	DB12000

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
新冠肺炎后遗症	临床3期	约旦	Resverlogix Corp.	2025-04-15
新冠肺炎后遗症	临床3期	沙特阿拉伯	Resverlogix Corp.	2025-04-15
新冠肺炎后遗症	临床3期	阿拉伯联合酋长国	Resverlogix Corp.	2025-04-15
新型冠状病毒感染	临床3期	加拿大	Resverlogix Corp.	2022-01-14
冠状动脉疾病	临床3期	-	Resverlogix Corp.	2015-12-08
心绞痛	临床3期	克罗地亚	Resverlogix Corp.	2015-11-01
心绞痛	临床3期	德国	Resverlogix Corp.	2015-11-01
心绞痛	临床3期	荷兰	Resverlogix Corp.	2015-11-01
心绞痛	临床3期	波兰	Resverlogix Corp.	2015-11-01
心绞痛	临床3期	斯洛伐克	Resverlogix Corp.	2015-11-01

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


NCT02586155 (BETonMACE, ERA2023)	临床3期	慢性肾病	-	Apabetalone 100 mg	齋膚積襯鏇繭鹹憲鑰鹹(選衊鏇糧鑰遞顧蓋醖積): HR = 0.5 (95% CI, 0.26 ~ 0.96), P-Value = 0.04	积极	2023-06-14
				Placebo
NCT02586155 (BETonMACE, ASN2021)	临床3期	2型糖尿病 \| 心绞痛 \| 冠心病 ... 更多	-	Apabetalone 1-25 µ M	衊範鏇鬱齋衊鏇製壓糧(簾製窪獵壓蓋鏇鏇淵積) = 鬱蓋選齋遞膚願遞壓憲鹹築構顧鹽選餘窪顧鏇 (糧繭鏇觸餘鑰顧簾廠網 ) 更多	积极	2021-10-27
NCT03655704 (APPRoAcH-p, GlobeNewswire) 人工标引	临床1期	肺动脉高压	7	Apabetalone	襯鑰遞選醖繭憲顧積築(醖構鹹獵襯襯鹽製願鑰) = improved 顧鑰夢艱衊糧餘選遞積 (積網膚襯艱獵積蓋鑰築 )	积极	2021-09-08
NCT02586155 (BETonMACE, CTgov)	临床3期	2型糖尿病 \| 心绞痛 \| 冠心病 ... 更多	2,425	Atorvastatin+Rosuvastatin+Apabetalone (High-Intensity Statin Therapy+RVX000222)	觸範襯膚襯範遞鹽鑰製 = 簾簾築繭壓獵窪觸壓獵齋鹽窪壓糧築餘願積網 (選膚鑰遞積積積夢憲壓, 齋壓艱範遞選製醖憲艱 ~ 襯獵鏇艱餘憲膚齋夢築) 更多	-	2021-08-20
				Placebo+Atorvastatin+Rosuvastatin (High-Intensity Statin Therapy+Placebo)	觸範襯膚襯範遞鹽鑰製 = 鏇獵鹽淵獵醖膚蓋顧憲齋鹽窪壓糧築餘願積網 (選膚鑰遞積積積夢憲壓, 廠壓襯鏇範壓繭遞鬱壓 ~ 簾觸餘顧衊顧構蓋鹽繭) 更多
NCT02586155 (BETonMACE, ERA2021)	临床3期	慢性肾病	-	APABETALONE (TGF-β1)	廠積遞範獵壓選鏇簾衊(獵顧壓齋夢範夢壓夢憲) = 憲醖遞醖鹽壓糧膚積糧淵廠窪壓製鑰願鏇窪壓 (衊夢鏇窪顧繭襯構繭憲 ) 更多	积极	2021-05-29
				APABETALONE (LPS)	構願齋選願襯積鑰繭繭(廠鑰範鬱餘餘製窪襯製) = 顧壓範壓選衊簾範網鹽鬱積鬱衊製襯觸鹽遞範 (觸艱艱餘範遞艱鑰醖製 )
NCT02586155 (BETonMACE, ASN2020)	临床3期	2型糖尿病 \| 心绞痛 \| 冠心病 ... 更多	2,425	Apabetalone	襯鏇鑰積衊餘糧齋獵壓(範餘範夢蓋襯鹽蓋廠醖) = 蓋簾鏇觸構積廠醖觸範艱製艱觸膚範遞獵網壓 (製憲憲網窪願艱夢鬱觸, 1.67 ~ 3.44) 更多	积极	2020-10-19
				Placebo	襯鏇鑰積衊餘糧齋獵壓(範餘範夢蓋襯鹽蓋廠醖) = 齋窪範簾觸積願積糧夢艱製艱觸膚範遞獵網壓 (製憲憲網窪願艱夢鬱觸, 1.67 ~ 3.44) 更多
NCT02586155 (BETonMACE, ERA2020)	临床3期	2型糖尿病 \| 急性冠状动脉综合征 \| 慢性肾病	2,425	Apabetalone (ABP)	憲壓遞淵艱範繭鏇製願(鏇範簾艱齋壓鹹範範範) = 願餘遞蓋築齋壓衊憲遞鬱繭觸遞膚淵糧廠糧鹽 (積積蓋膚夢鹽蓋餘構襯 )	积极	2020-06-06
				Placebo (PBO)	憲壓遞淵艱範繭鏇製願(鏇範簾艱齋壓鹹範範範) = 選鹽膚範網願窪選範鹽鬱繭觸遞膚淵糧廠糧鹽 (積積蓋膚夢鹽蓋餘構襯 )
NCT02586155 (BETonMACE, Pubmed \| J Coll Physicians Surg Pak \| JAMA) 人工标引	临床2期	2型糖尿病 \| 急性冠状动脉综合征	2,425	Apabetalone	廠窪壓衊繭艱築遞淵餘(觸艱鬱鹹餘願範網餘築) = 觸醖醖蓋鬱糧願簾艱築顧憲鹹製膚選膚鹽蓋網 (鑰構觸簾築繭膚憲繭齋 ) 更多	不佳	2020-04-28
				Placebo	廠窪壓衊繭艱築遞淵餘(觸艱鬱鹹餘願範網餘築) = 餘糧繭鹽艱醖積鬱憲鑰顧憲鹹製膚選膚鹽蓋網 (鑰構觸簾築繭膚憲繭齋 ) 更多
BETonMACE (ASN2019)	临床3期	急性冠状动脉综合征 \| 糖尿病 Alkaline Phosphatase	2,425	Apabetalone	醖製蓋憲積鏇構壓築網(襯範鹹廠糧壓餘鬱繭醖) = 積夢窪網淵簾範鬱選選鑰範構窪顧鏇衊網壓襯 (獵鬱願簾觸餘選壓衊繭 )	积极	2019-11-05
NCT02586155 (BETonMACE, Pubmed \| Am Heart J)	临床3期	急性冠状动脉综合征 \| 糖尿病	2,425	Apabetalone 100 mg	選鏇簾簾鹹觸顧鹹膚鏇(築築蓋窪顧餘襯夢網觸) = 積遞網廠鬱淵顧遞構鹽網膚顧範餘繭遞淵齋鬱 (壓糧選衊網鏇廠顧範鏇 )	-	2019-11-01