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

/ Not yet recruiting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

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100 项与 Apabetalone 相关的临床结果

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100 项与 Apabetalone 相关的转化医学

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100 项与 Apabetalone 相关的专利（医药）

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180

项与 Apabetalone 相关的文献（医药）

2025-04-11·ACS Pharmacology & Translational Science

Orally Bioavailable BRD4 BD1 Inhibitor ZL0516 Effectively Suppresses Colonic Inflammation in Animal Models of Inflammatory Bowel Disease

Article

作者: Panganiban, Ronaldo P. ; Cong, Yingzi ; He, Jing ; Yang, Wenjing ; Brasier, Allan R. ; Pinchuk, Irina V. ; Liu, Zhiqing ; Yochum, Gregory ; Tian, Bing ; McAninch, Steven ; Chen, Haiying ; Ma, Zonghui ; Zhang, Cun ; Zhou, Jia

Inflammatory bowel disease (IBD), a chronic, progressive, and recurrent gastrointestinal inflammatory disorder, poses a significant threat to global health and exerts an adverse effect on the quality of life. Currently, there is a lack of effective therapies for IBD. Developing novel targeted therapies for IBD, particularly orally effective therapeutics, is a vital need for IBD patients. Herein, we first demonstrate that BRD4/NF-κB signaling is aberrantly activated in the colons of human IBD biopsy samples compared to that of normal healthy controls. ZL0516, a potent, selective, and orally bioavailable BRD4 BD1 inhibitor, significantly inhibits the TNFα- and LPS-induced expression of inflammatory cytokines in human colonic epithelial cells (HCECs) and peripheral blood mononuclear cells (PBMCs) with low cytotoxicity. Intriguingly, when administered in a preventive mode, ZL0516 significantly blocks dextran sulfate sodium (DSS)-induced murine colitis. When used in a therapeutic mode, ZL0516 effectively suppresses colonic inflammation in several IBD-relevant animal models: DSS-, oxazolone (OXA)-, and flagellin (Cbir1) T cell-induced chronic murine colitis models of IBD. ZL0516 suppresses IBD inflammatory responses in vitro and in vivo by blocking the activation of the BRD4/NF-κB signaling pathway. Also, we found that RVX208, a selective BRD4 BD2 inhibitor in Phase III clinical development, only displayed marginal effects in these IBD animal models. Collectively, our results demonstrate that specific BRD4 BD1 inhibition is a novel therapeutic strategy for IBD-associated colonic inflammation, and orally effective inhibitor ZL0516 is a promising candidate for the development of a novel therapeutic regimen against IBD.

2025-03-01·VIROLOGY

A high-throughput, microplate reader-based method to monitor in vitro HIV latency reversal in the absence of flow cytometry

Article

作者: Nkwelle, Chantal Emade ; Esemu, Seraphine N ; Ndip, Roland N ; Liang, Kimberly ; Ntie-Kang, Fidele ; Tietjen, Ian ; Cassel, Joel ; Stephens, Unique ; Salvino, Joseph M ; Montaner, Luis J

J-Lat cells are derivatives of the Jurkat CD4⁺ T cell line that contain a non-infectious, inducible HIV provirus with a GFP tag. While these cells have substantially advanced our understanding of HIV latency, their use by many laboratories in low and middle-income countries is restricted by limited access to flow cytometry. To overcome this barrier, we describe a modified J-Lat assay using a standard microplate reader that detects HIV-GFP expression following treatment with latency-reversing agents (LRAs). We show that HIV reactivation by control LRAs like prostratin and romidepsin is readily detected with dose dependence and with significant correlation and sensitivity to standard flow cytometry. For example, 10 μM prostratin induced a 20.1 ± 3.3-fold increase in GFP fluorescence in the microplate reader assay, which corresponded to 64.2 ± 5.0% GFP-positive cells detected by flow cytometery. Similarly, 0.3 μM prostratin induced a 1.7 ± 1.2-fold increase compared to 8.7 ± 5.7% GFP-positive cells detected. Using this method, we screen 79 epigenetic modifiers and identify CUDC-101, molibresib, and quisinostat as novel LRAs. This microplate reader-based method offers accessibility to researchers in resource-limited regions to work with J-Lat cells and more actively participate in global HIV cure research efforts.

2025-03-01·INTERNATIONAL IMMUNOPHARMACOLOGY

Apabetalone alleviates ligature-induced periodontitis by inhibiting M1 macrophage polarization via an immunometabolic shift

Article

作者: Zhang, Yiding ; Liu, Haohao ; Bian, Tianying ; Li, Hu ; Guo, Mudi ; Chen, Meihua ; Hu, Pinli

OBJECTIVES:

To explore the effects and biological mechanism of apabetalone on periodontal inflammation by regulating glycolysis and metabolites.

METHODS:

A ligature-induced periodontitis model was established in mice and apabetalone was administered on the ligation silk for two weeks. Inflammation levels and alveolar bone absorption were explored using micro-computed tomography and histopathological analysis. To observe the role of apabetalone in macrophage polarization and the macrophage-mediated immune microenvironment, a Luminex assay, quantitative real-time polymerase chain reaction, a conditioned medium experiment, a Seahorse extracellular flux assay and quantitative metabolomics were used for molecular biological analysis.

RESULTS:

Apabetalone-treated mice exhibited ameliorated alveolar bone loss and inflammatory infiltration in the periodontium. Furthermore, apabetalone significantly inhibited the production of proinflammatory cytokines and suppressed the levels of M1-specific biomarkers both in vivo and in vitro. Apabetalone also promoted the osteogenic potential of mouse periodontal ligament cells in a macrophage-mediated microenvironment. Apabetalone restrained LPS-induced glucose uptake and lactic acid production. Apabetalone inhibited glycolysis by suppressing the transcription and protein expression of hexokinase 2, glucose transporter 1 and phosphofructokinase-2/fructose-2,6- bisphosphatase 3 (PFKFB3) in a dose-dependent manner. Quantitative analysis of certain carbohydrates involved in energy metabolism revealed that apabetalone reserved the disruption of the tricarboxylic acid (TCA) cycle and inhibited glycolysis and the pentose phosphate pathway. In addition, apabetalone increased the oxygen consumption rate.

CONCLUSION:

Collectively, these findings indicate that apabetalone improves the periodontal immune microenvironment by regulating metabolites in macrophages. Apabetalone exerts anti-inflammatory and osteo-protective effects by replenishing the broken TCA cycle and suppressing glycolysis. Apabetalone is a potential candidate for the treatment of periodontitis.

项与 Apabetalone 相关的新闻（医药）

2025-04-05

·药融圈

海普瑞逆袭战报：从巨亏7.8亿到盈利6.5亿！CDMO业务爆发，全球化战略全面提速

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。业绩亮点：逆境突围，盈利质量显著提升2025年3月，海普瑞发布2024年年度报告，全年实现营业收入52.81亿元，同比微降3.03%；归母净利润6.47亿元，同比大幅扭亏（2023年亏损7.83亿元），扣非净利润2.54亿元，同比增长132.51%。经营活动现金流净流入21.94亿元，同比激增450.99%，资产负债率优化至29.64%，财务韧性显著增强。核心驱动因素：制剂业务全球市占率提升：依诺肝素钠制剂全年销量突破2333万支，同比增长13.31%，欧洲市场份额稳居前二，美国市场通过自营与代理双模式实现高速增长，中国市场依托集采政策销量攀升，非欧美市场新增泰国、新西兰准入。原料药业务量升价稳：肝素钠原料药销量同比增长10.82%，尽管行业价格承压，但公司通过聚焦成熟法规市场、优化客户结构，实现毛利率同比提升8.66个百分点至29.36%。CDMO业务高增长：赛湾生物与SPL双平台协同发力，收入同比增长6.91%至10.34亿元，毛利率提升13.8个百分点至35.83%，新客户拓展与项目储备为后续增长奠定基础。业务拆解：三驾马车协同，全球化布局深化1.肝素产业链：制剂扛旗，全链条韧性凸显制剂业务：收入29.86亿元，占比56.55%，毛利率33.60%。欧洲市场通过本地化团队深耕，持续中标主流国家采购；美国市场福沙匹坦二葡甲胺商业化推进顺利；中国市场依托集采实现量增，同时探索院外市场新增长点。原料药业务：收入10.69亿元，销量增长10.82%，毛利率提升至29.36%。公司通过全球供应链布局和成本控制，抵御行业价格下行压力，销量逆势增长。2.CDMO业务：双平台协同，高毛利赛道提速赛湾生物：聚焦生物大分子及基因治疗领域，客户覆盖全球药企，2024年新增项目超百个，产能利用率稳步提升。SPL：强化天然药物提取技术优势，与赛湾形成互补，共同支撑CDMO收入增长至10.34亿元，毛利率同比提升13.8个百分点，盈利能力显著增强。3.创新药与投资：管线突破，资本运作优化自研管线：H1710（抗乙酰肝素酶抑制剂）获临床试验批准，用于实体瘤治疗；BD合作：通过股权投资持有20余个创新药品种大中华区权益，其中3款进入全球III期临床，RVX-208等品种商业化推进顺利；投资收益：通过优化资产配置，全年投资收益1.96亿元，公允价值变动收益1.31亿元，有效增厚利润。未来展望：技术赋能全球化，三大战略路径清晰1.制剂业务：从“中国份额”到“全球品牌”市场扩张：加速东南亚、拉美等新兴市场准入，2025年计划新增3-5个国家注册；产品升级：推进依诺肝素钠预充式注射器等新剂型研发，提升差异化竞争力。2.CDMO业务：产能与技术双轮驱动产能布局：美国、欧洲基地扩产项目推进，2025年计划新增20%产能；技术突破：深化mRNA、细胞基因治疗等新兴领域工艺开发，拓展高附加值服务。3.创新药：聚焦临床需求，打造第二增长曲线自研管线：H1710启动I期临床，布局肝癌、胰腺癌等适应症；外部合作：与正大天晴等药企深化合作，推动中国创新药出海欧美市场。结语：从行业龙头到创新引领者海普瑞2024年的成绩单，展现了其在复杂环境中的战略定力与执行效率。通过肝素产业链的全球化深耕、CDMO业务的技术突破，以及创新药管线的前瞻性布局，公司正从传统原料药企业向“研发+制造+商业化”全链条服务商转型。来源：海普瑞2024年报、原料药情报局整理版权声明：本文转自原料药情报局，如不希望被转载的媒体或个人可与我们联系，我们将立即删除植根上海、辐射全球,药融圈作为生物医药产业级战略平台,以"让智慧与人脉无界流动"为使命,构建覆盖药物研发、生产、流通、商业化的全产业链赋能体系。通过智能化云服务、精准资源链接、产业智库与生态社群四大核心引擎,打造中国医药价值流动的基础设施。在全球化与数字化双重浪潮下,药融圈正重新定义医药资源的流通范式--这里不仅是信息与人脉的枢纽站,更是催生产业变革的化学反应器。我们以中国为原点,编织全球医药智慧网络,让每一次精准链接都成为企业跨越式增长的催化剂。点点赞点分享点推荐

财报基因疗法临床3期

2025-03-25

·精准药物

BET 溴结构域抑制剂研发现状与挑战

赖氨酸乙酰化为 BET溴结构域(BET bromodomain)蛋白的表观遗传读取域创建了对接位点，而这些蛋白已成为特异基因转录的主要调节剂。BET 抑制剂历经了泛 BET 抑制剂，到选择性的第二代抑制剂，以及高效的双功能和双重抑制剂。 1. 背景介绍 ω-氮赖氨酸残基的乙酰化是染色质结构的关键调节因子，该过程的失调与多种疾病的发展有关。组蛋白乙酰化是表观遗传密码的主要组成部分，控制基因进入转录机制的可及性，因此它受到两个酶家族作用的严格控制：“写入”乙酰化标记的组蛋白乙酰转移酶 (HAT) ，或“擦除”这些修饰的组蛋白去乙酰化酶 (HDAC)。HDAC 已成为主要的药物靶点，凸显了控制异常转录作为治疗策略的重要性。乙酰化标记由溴结构域家族的表观遗传读取结构域特异性识别，该家族构成了人类蛋白质组中 61 个不同的结构保守的蛋白质相互作用结构域。 BET 家族由人类的四个成员（BRD2、BRD3、BRD4 和 BRDT）组成，每个成员都含有两个 N 端溴结构域（BD1、BD2）。将 pTEF 募集到转录活性的组蛋白乙酰化基因启动子上，在控制基础转录机制方面发挥着重要作用。重要的是，BET 蛋白是控制特异性转录的关键调节因子，它通过介导（超级）增强子中的蛋白质相互作用来控制特异性转录。十多年前，人们发现了有效的溴结构域抑制剂，并且有望控制包括不可药用转录因子（如致癌基因 MYC）等致病基因家族，这促使人们开发出各种 BET 抑制剂，并针对该靶标家族开展临床研究。本文，总结了BET 抑制剂的最新进展及潜力。 pan-BET选择性抑制剂 2005 年，已鉴定出首批与溴结构域 (BD) 的乙酰赖氨酸 (KAc) 结合位点结合的骨架，其靶向乙酰赖氨酸转移酶 PCAF 的溴结构域，但在鉴定出首批强效且具有选择性的抑制剂后才开始迅速发展。3-methyltriazolothienodiazepines和methyltriazolobenzodiazepines是首批强效且具有选择性的泛 BET 抑制剂。结构研究表明，这些抑制剂与 BET 溴结构域的乙酰赖氨酸结合位点结合（图 1a）。三唑环充当乙酰赖氨酸模拟部分，通过模拟乙酰赖氨酸羰基与保守的天冬酰胺残基（BRD4 BD1 中的 N140）形成的氢键，以及与保守的酪氨酸（BRD4 BD1 中的 Y97）形成的水介导氢键。BET 溴结构域中还保留了一个结构水网络，从 Y97 延伸到乙酰赖氨酸结合位点和 ZA 通道的底部（图 1b）。3-methyltriazolothienodiazepines已被广泛用于设计溴结构域抑制剂，通常是通过对溶剂暴露区域进行修改（图 1c）。基于片段的发现和计算机模拟揭示了乙酰赖氨酸模拟片段的多样性，这表明 BET 溴结构域具有很好可成药性。含有二甲基异恶唑核心的片段产生了多种新型泛 BET 抑制剂，包括有效的工具分子，如 iBET151 和 PLX51107、亚纳摩尔抑制剂 HJB97、以及 I-BET282E和 CPI-0610。此外，其他五元环体系，包括 4-methyl 1,2,3 triazoles和 2-thiazolidinones。结构域选择性抑制剂人 BET 溴结构域的高度序列同源性使结构域特异性抑制剂的开发具有挑战性，但最近的研究表明，通过小分子靶向第一个 BD1或第二个 BD2　溴结构域是可行的。RVX-208 与 BET 溴结构域的共晶体结构表明，RVX-208 与溶剂暴露残基相互作用，这些残基在 BD2 溴结构域内是保守的，但在 BD1 溴结构域中有所不同。在最近开发的 BD2 选择性抑制剂 ABBV-744（图 2a、b）中，已经探索了这些残基变异，特别是BRD2 中的 H433、 D160、P430 和 K158。反过来，通过优化与 BD1 独特的 BC 环中天冬氨酸-赖氨酸残基的相互作用，实现了 BD1 选择性。葛兰素史克公司证明，可以利用针对 BD1 和 BD2 之间不同的残基来开发高选择性的 BD1 和 BD2 抑制剂（图 2c、d）。 BD1 和 BD2 选择性抑制剂显示出显著的表型差异和对基因转录的不同影响。BD1 选择性抑制剂对癌细胞系和 mRNA 转录具有与泛 BET 抑制剂相似的广泛活性。相比之下，ABBV-744 仅在某些癌细胞中表现出抗增殖作用。例如，在前列腺癌细胞系中，ABBV-744 选择性地将 BRD4 从含 AR 的超增强子中置换出来，从而抑制了 AR 依赖性转录。然而，使用高 BD2 选择性抑制剂 iBET-BD2 并未观察到从启动子或增强子区域的置换，该抑制剂对改变预先存在的基因表达程序的影响很小，但阻断了驱动快速基因表达程序诱导的刺激反应。双功能活性(BET+激酶) 抑制剂 BET 溴结构域是激酶抑制剂的常见脱靶物。两种高度多样化的靶标类别之间令人惊讶的交叉反应表明乙酰赖氨酸模拟部分在类药分子中很常见，这凸显了溴结构域出色的成药性。虽然临床激酶抑制剂（如 PLK1 抑制剂 BI-2536）的 BET 活性明显较弱，但随后对这些双重抑制剂进行优化，产生了具有平衡双靶标活性的化合物或由这些双重活性化合物衍生的选择性 BET 抑制剂。一些激酶抑制剂的 BET 活性也表明，这种双重活性可以合理设计用于治疗严重依赖两种靶标的疾病。这种想法导致了例如 ALK-BET 或 JAK-BET 双重抑制剂的出现。在胰腺导管腺癌 (PDAC) 等难以治疗的癌症中，BET 和 HDAC 靶点类别之间存在协同作用，以此理性设计了第二类的双重抑制剂。将 HDAC 抑制剂 Vorinostat 和泛 BET 抑制剂 JQ1 结合起来，在 PDAC 细胞系中表现出协同作用，诱导细胞凋亡，并抑制 KRAS 突变小鼠的癌前病变，显著减少体内肿瘤体积，并且没有复发的迹象。从机制层面上讲，在 PDAC 中经常被沉默的 p57 (Cdkn1c) 在用两种抑制剂处理的细胞中协同去抑制。事实上，早期概念验证抑制剂（如 JQ1 衍生物与 I 类 HDAC 抑制剂 CI994 (TW9)）在体外表现出显著的协同作用，可抑制胰腺癌细胞生长。因此，BET 抑制剂与其他类别靶标的合理组合，可以显著降低体内实现显著抗肿瘤活性所需的 BET 抑制剂剂量。双结构域抑制剂 BET 蛋白中存在两个相邻的溴结构域，这表明可以开发双功能抑制剂 (biBET) 来同时靶向 BD1 和 BD2。通过简单地将两个 JQ1 分子与基于 PEG 的连接体连接而开发的。与相应的单价抑制剂相比，所得抑制剂 MT1 的效力提高了约 100 倍。类似的设计思路促成了 MS654，它显示出对乳腺癌中 BRD4 的持续抑制。药代动力学优化使 AZD5153（图 3a，临床II期，AML）具有出色的体内效力。然而，AZD5153 中使用两种不同的乙酰赖氨酸模拟部分，3-methoxy-triazolo pyridazine和1,3 dimethylpiperazine-2-one，也导致溴结构域家族中存在一些脱靶活性。第二类双功能抑制剂提高了 BET 家族的选择性，它们利用手柄与 E3 连接酶结合，将靶标募集到泛素蛋白酶体系统中，导致其药物诱导的降解。第一个 BET PROTAC，称为 dBET1，使用泛 BET 抑制剂 JQ1 和沙利度胺衍生物作为 E3 连接酶手柄开发，导致有效和选择性降解白血病细胞中表达的所有 BET 家族成员（BRD2-4）并强烈降解 MYC 水平。有趣的是，与 VHL 配体 VH032 连接 JQ1 的 PROTAC：MZ1(图 3b)，其显示 BRD4选择性降解。该结构得到三元复合物（VHL-MZ1-BRD4）结构的理性解释。结果表明将 E3 募集到靶标并，与接头的优化导致靶标特异性降解，该策略可能允许降解具有组织特异性功能的其他 BET 异构体。组织或疾病特异性 E3 的配体的选择将导致 BET 家族中个别成员的限制性降解。然而，需要开发这些 E3 的新配体。临床研究 BET 抑制剂对多种癌症的疗效进行临床研究。除了 NMC（一种罕见的癌症，其睾丸特异性蛋白 NUT 与 BRD3 或 BRD4 发生重排）外，大多数临床试验并未针对特定的分子亚型，这表明需要进行生物标志物研究，以确定决定抑制剂敏感性和耐药性的标志物。由于其高度依赖于 NUT-BRD3/4 融合致癌基因，因此人们对使用泛 BET 抑制剂治疗这种侵袭性癌症的期望很高。然而，虽然在一些 NMC 患者中观察到部分反应，但用 BET 抑制剂治疗这种癌症并未达到基于令人信服的临床前数据的预期，原因仍有待阐明。可能由于剂量限制性副作用（例如血小板减少、贫血、中性粒细胞减少、胃肠道事件和疲劳）导致患者无法达到治疗所需的剂量。BD2 选择性抑制剂或降低抑制剂剂量的联合疗法可能会产生更强劲的临床反应，尤其是当针对导致 BET 抑制剂耐药的途径时。此外，AZD5153 等双功能抑制剂现已进入临床试验（NCT03205176，临床II期，2021-03-08），分子降解剂领域的快速进展使得针对 PROTAC 的 BET 抑制剂也有望很快进入临床研究。 BET溴结构域家族是非常火热的研发方向，特别是RBD4，以此开发了许多抑制剂。泛BET抑制剂的首次临床数据显示，剂量限制毒性、适度的抗肿瘤活性。除了开发更有效的抑制剂/降解剂，明确生物作用机制，未来还特别需要明确特异的临床适应症和生物标志物。PMID: 35462054 声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

申请上市临床结果临床2期

2024-05-28

·BioSpace

Resverlogix Announces Updated Annual and Special Meeting of Shareholders

Calgary, Alberta--(News - May 28, 2024) - Resverlogix Corp. (TSX: RVX) ("Resverlogix" or the "Company") announced today that its Annual and Special Meeting of Shareholders (the "Meeting") will be held on Wednesday, July 31, 2024, commencing at approximately 1:00 pm (MT), as opposed to as previously scheduled for June 27, 2024. A Notice of Meeting and Management Information Circular, containing the matters to be considered at the Meeting, will be delivered to shareholders and filed on SEDAR+ at . Following the formal business of the Meeting, a corporate update presentation will be provided. About Resverlogix 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 has partnered with EVERSANA™, the pioneer of next generation commercial services to the global life sciences industry, to support the rapid commercialization of apabetalone for cardiovascular disease, post COVID-19 conditions, and pulmonary arterial hypertension in Canada and the United States. Resverlogix common shares trade on the Toronto Stock Exchange (TSX: RVX). Follow us on: Twitter: @Resverlogix_RVX LinkedIn: Forward-Looking Statements: 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 upcoming Annual and Special Meeting of Shareholders and 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 . 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 Or visit our website: To view the source version of this press release, please visit

100 项与 Apabetalone 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11131	Apabetalone	-	DB12000

研发状态

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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
冠心病	临床3期	阿根廷	Resverlogix Corp.	2015-11-01
冠心病	临床3期	澳大利亚	Resverlogix Corp.	2015-11-01
冠心病	临床3期	比利时	Resverlogix Corp.	2015-11-01
冠心病	临床3期	保加利亚	Resverlogix Corp.	2015-11-01
冠心病	临床3期	克罗地亚	Resverlogix Corp.	2015-11-01
冠心病	临床3期	德国	Resverlogix Corp.	2015-11-01

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临床结果

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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


NCT02586155 (BETonMACE, ERA2023)	临床3期	慢性肾病	-	Apabetalone 100 mg	糧艱襯獵簾觸膚觸範壓(壓淵鑰鏇蓋鏇淵壓鹹壓): 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 \| 冠心病	-	Apabetalone 1-25 µ M	糧鏇鏇壓網觸選淵簾廠(繭夢遞鬱繭艱觸構蓋構) = 廠願壓艱醖簾獵醖製遞願製淵醖製餘遞夢願簾 (鏇鑰廠餘鏇積夢積鏇夢 ) 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	糧簾蓋選齋壓艱遞廠築(遞獵蓋觸壓範蓋鹽醖鏇) = improved 襯鹽窪積衊淵餘築繭鹹 (範餘醖鬱鏇獵願夢範網 )	积极	2021-09-08
NCT02586155 (BETonMACE, CTgov)	临床3期	2型糖尿病 \| 冠心病	2,425	rosuvastatin+atorvastatin+Apabetalone (High-Intensity Statin Therapy+RVX000222)	遞鬱廠艱壓夢構願鹹繭 = 鏇鑰糧窪鬱廠鹽網積廠艱選壓糧繭選壓獵醖簾 (壓遞觸艱築鹹觸願範鏇, 窪醖選艱獵製醖構鑰遞 ~ 夢簾積選壓簾壓蓋顧壓) 更多	-	2021-08-20
				Placebo+rosuvastatin+atorvastatin (High-Intensity Statin Therapy+Placebo)	遞鬱廠艱壓夢構願鹹繭 = 網選鏇範襯窪鏇繭廠齋艱選壓糧繭選壓獵醖簾 (壓遞觸艱築鹹觸願範鏇, 願願觸淵齋範淵選製襯 ~ 艱觸醖選艱夢鹽齋衊窪) 更多
NCT02586155 (BETonMACE, ERA2021)	临床3期	慢性肾病	-	APABETALONE (TGF-β1)	積鹽顧淵艱壓鏇艱窪選(窪觸衊網襯遞齋繭範淵) = 襯簾網繭簾構築遞構膚鏇艱簾築壓襯鹽壓鏇網 (積膚築襯觸醖鏇鑰鹽積 ) 更多	积极	2021-05-29
				APABETALONE (LPS)	繭積窪窪襯廠獵簾選餘(膚衊鹽窪衊簾糧壓艱蓋) = 艱範糧淵鹹餘夢齋糧淵獵顧壓齋鏇齋築襯鹹鬱 (觸獵艱製衊獵鑰遞鏇蓋 )
AAI2021	N/A	法布里病	-	Apabetalone	鏇夢獵觸壓艱築憲構鏇(艱觸夢醖願網糧積鬱顧) = 膚選顧願襯憲積獵簾簾鹹淵鹹艱築廠衊襯鬱願 (艱網顧繭遞選膚醖範鬱 )	-	2021-05-01
NCT02586155 (BETonMACE, ASN2020)	临床3期	2型糖尿病 \| 冠心病	2,425	Apabetalone	壓鬱願憲膚獵遞鏇餘夢(艱襯餘顧遞願襯製廠廠) = 艱製齋鏇蓋鑰鏇鑰壓構膚顧遞簾膚餘築選餘夢 (選構願獵願糧鹹醖齋窪, 1.67 ~ 3.44) 更多	积极	2020-10-19
				Placebo	壓鬱願憲膚獵遞鏇餘夢(艱襯餘顧遞願襯製廠廠) = 廠壓齋淵衊積製齋夢膚膚顧遞簾膚餘築選餘夢 (選構願獵願糧鹹醖齋窪, 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)	鑰衊衊蓋醖製齋顧鬱積(願積繭願網築鬱餘觸顧) = 窪壓積遞餘鹽夢蓋顧獵醖衊憲鹽鏇夢廠醖憲齋 (齋餘憲鑰網糧鏇鏇鏇觸 )	积极	2020-06-06
				Placebo (PBO)	鑰衊衊蓋醖製齋顧鬱積(願積繭願網築鬱餘觸顧) = 選選醖淵壓遞選夢製壓醖衊憲鹽鏇夢廠醖憲齋 (齋餘憲鑰網糧鏇鏇鏇觸 )
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	齋夢餘衊簾艱遞選繭蓋(鹽膚衊膚獵鏇網築繭鏇) = 範壓襯膚鬱遞鹹壓鹽繭膚鑰網壓襯壓獵築憲衊 (製糧製範鑰積夢壓鹽蓋 ) 更多	不佳	2020-04-28
				Placebo	齋夢餘衊簾艱遞選繭蓋(鹽膚衊膚獵鏇網築繭鏇) = 顧醖餘築製衊醖網範壓膚鑰網壓襯壓獵築憲衊 (製糧製範鑰積夢壓鹽蓋 ) 更多
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	鹽願衊鹹壓齋糧蓋廠顧(鹽襯繭襯範餘壓製襯繭) = 壓艱範顧鏇簾獵繭衊壓選艱艱願鏇餘艱獵範繭 (遞構壓鹽觸鹹鑰鬱繭獵 )	-	2019-11-01