A Multi-center, Randomized, Double-Blind, Parallel-group, Vehicle-Controlled Study to Evaluate the Safety, Efficacy and Pharmacokinetics of DFD-25 (Zileuton Ointment), 1.25% and 5%, in Subjects with Moderate to Severe Atopic Dermatitis (AD) Over a 4 Week Treatment Period

开始日期2019-12-02

申办/合作机构-

NCT03571620

/ Completed临床2期

A Multicenter, Randomized, Phase 2, Double-blind, Vehicle-controlled, Parallel Group Comparison Study to Evaluate the Safety and Efficacy of Q301 Cream in Adolescents and Adults With Mild to Moderate Atopic Dermatitis

This is a randomized, double-blind, vehicle-controlled, parallel-group comparison study to evaluate the safety and efficacy of Q301 Cream vs. vehicle in adolescent and adult subjects with mild to moderate AD. Study drug (Q301 Cream or vehicle) will be administered topically twice a day for 8 consecutive weeks.

开始日期2018-06-21

申办/合作机构

Qurient Co., Ltd.

NCT02348203

/ Completed临床2期IIT

Clinical Study of the Effect of Combined Treatment of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers

This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers.

开始日期2016-01-13

申办/合作机构

National Cancer Institute

100 项与齐留通相关的临床结果

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100 项与齐留通相关的转化医学

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100 项与齐留通相关的专利（医药）

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项与齐留通相关的文献（医药）

2026-03-01·FREE RADICAL BIOLOGY AND MEDICINE

Inhibiting Arachidonate-5-lipoxygenase expression ameliorates osteoarthritis progression by suppressing ferroptosis via the JAK2/STAT3 signaling pathway

Article

作者: Zhang, Kaiming ; Sun, Xianding ; Yao, Xudong ; Zou, Fuzheng ; Cheng, Xingwang ; Wang, Ting ; Nie, Mao ; Shi, Lei ; Kuang, Biao

BACKGROUND:

Osteoarthritis (OA) is a degenerative joint disease. Recent studies have shown that ferroptosis plays a critical role in OA. Arachidonate-5-lipoxygenase (ALOX5), a pivotal enzyme regulating arachidonic acid metabolism, is involved in the synthesis of the pro-inflammatory leukotrienes. However, its role in ferroptosis and OA has not been elucidated.

METHODS:

Measuring the expression of ALOX5 and ferroptosis-related markers in human cartilage and synovial fluid. Constructed small interfering RNA or plasmids were used to knockdown or overexpress Alox5 to explore its role in chondrocyte. Transcription factors regulating Alox5 were predicted through database analysis, while RNA sequencing revealed signaling pathways modulated by Alox5. Subsequently, the role of ALOX5 in destabilization of medial meniscus (DMM) OA model was investigated by intra-articular injection of knockdown (AAV-ShAlox5) or overexpression (AAV-OEAlox5) adeno-associated virus. Finally, the therapeutic efficacy of ALOX5 inhibitor Zileuton, was verified in vivo and in vitro.

RESULTS:

We observed upregulated ALOX5 expression in human cartilage and Alox5 knockdown mitigated IL-1β- and FAC-induced chondrocyte damage by suppressing ferroptosis. Through database predictive analysis and experimental verification, ALOX5 was modulated by the JNK-p53 signaling axis. Through RNA-seq analysis, it was found that knockdown of Alox5 inhibited the activation of the JAK2-STAT3 signaling pathway, thereby delaying the process of ferroptosis and slowing down the wear of articular cartilage. In the mouse DMM model, intra-articular injection AAV-ShAlox5 delayed DMM-induced cartilage degeneration, whereas AAV-OEAlox5 exacerbated cartilage damage. Similarly, treatment with Zileuton alleviated ferroptosis and chondrocyte injury,demonstrating a protective effect in vivo and in vitro.

CONCLUSIONS:

In summary, our study demonstrated knockdown of Alox5 inhibited the JAK2/STAT3 signaling, thereby suppressing ferroptosis and alleviating cartilage damage. Intra-articular injection of the ALOX5 inhibitor Zileuton or AAV-ShAlox5 in the knee joint alleviated cartilage damage in the mouse DMM model. Mechanistically, our study reveals that the JNK-p53-ALOX5 signaling axis alleviates OA by regulating ferroptosis in chondrocytes.

2026-02-01·MOLECULAR DIVERSITY

Novel pyrazole carboxylate derivatives as lonazolac bioisosteres with selective COX-2 inhibition: design, synthesis and anti-inflammatory activity

Article

作者: Nemr, Mohamed T M ; Amin, Dina M E ; Fadaly, Wael A A ; Abdelhady, Hoda Khalifa ; Abusabaa, Ahmed H A ; Mahmoud, Asmaa M ; Ibrahim, Nashwa A ; Elshewy, Ahmed ; Haredy, Haredy Hassan

Abstract:

Two novel series of di-aryl/tri-aryl substituted pyrazole ester derivatives 15a-h and 19a-d were designed, synthesized as novel non-acidic lonazolac analogs and tested for its COX-2, 5-LOX, 15-LOX, iNOS , pro-inflammatory cytokines TNF-α and PGE2 inhibitory activities. All the tested compounds showed excellent COX-2 inhibitory activity (IC 50 = 0.059–3.89 μM), compared to that of celecoxib (IC 50 = 0.22 μM), where derivatives 15c, 15d, 15 h and 19d were found to be the most potent showing COX-2 selectivity index in range of (S.I. = 28.56–98.71) compared to celecoxib (S.I. = 13.65). Moreover, the most potent four derivatives 15c, 15d, 15 h and 19d showed outstanding 5-LOX and 15-LOX inhibitory activities (IC 50 = 0.24–0.81, 0.20–2.2 respectively, compared to zileuton IC 50 = 1.52 and 0.54, respectively). Further investigation of the anti-inflammatory mechanistic study of derivatives 15c, 15d, 15 h and 19d revealed that these four compounds exhibited comparable TNF-α and PGE2 (LPS-induced pro-inflammatory cytokines) inhibitory activities (IC 50 = 0.77–1.20 μM and 0.28–0.52 μM respectively) when compared to celecoxib (IC 50 = 0.87 μM and 0.38 μM respectively) as reference drug using lipopolysaccharide-activated RAW 264.7 macrophages. Based on the advanced inhibitory activity of compounds 15c, 15d, 15 h and 19d against LPS-induced pro-inflammatory mediators (TNF-α and PGE2), inducible nitric oxide synthase (iNOS) inhibition assay was carried out. Remarkably, compounds 15c, 15d, 15 h and 19d showed higher potency with lower IC 50 (0.41–0.61 µM) when compared to the reference drug celecoxib (0.48 µM). Prior to in vivo anti-inflammatory activity screening, cytotoxicity testing was performed to ascertain safe and non-toxic concentrations of each compound. Safe doses of compounds were determined using lipopolysaccharide-activated RAW 264.7 macrophages, moreover results showed that compounds 15c, 15d, 15 h and 19d were more safer (less cytotoxic) with higher IC 50 (178.95–301.40 µM) when compared to the reference drug celecoxib (148.90 µM). In vivo anti-inflammatory activity of the target compounds 15c, 15d, 15 h and 19d reinforced the results of in vitro screening as the derivatives 15c, 15d, 15 h and 19d showed (ED 50 = 8.22–31.22 mg/kg, respectively) and were more potent than celecoxib (ED 50 = 40.39 mg/kg). All screened derivatives 15c, 15d, 15 h and 19d were less ulcerogenic (ulcer indexes = 1.22–3.93) than lonazolac (ulcer index = 20.30) and comparable to celecoxib (ulcer index = 3.02). In silico docking and ADME studies were carried out in order to clarify the interactions of the most active derivatives 15c, 15d, 15 h and 19d with the target enzymes and their pharmacokinetic parameters.

2026-01-01·DRUG METABOLISM AND DISPOSITION

Zileuton nanocrystals alter intestinal phase I/II metabolic enzymes and epithelial permeability in a sex-dependent manner

Article

作者: Khare, Sangeeta ; Gokulan, Kuppan ; Burgess, Diane J ; Yanamadala, Yaswanthi ; Harris, Kenneth James

The bioavailability of a drug is influenced by its physicochemical properties, dissolution rate, solubility, gastrointestinal tract permeability, and its absorption, distribution, and metabolism. Zileuton, a poorly soluble biopharmaceutical classification system class II drug prescribed for the treatment of asthma, was selected as a candidate for nanocrystal drug formulation. Our previous study demonstrated that zileuton nanocrystal formulation (NfZ) efficiently suppressed proinflammatory cytokines associated with asthma pathogenesis. Hence, this study aims to evaluate whether sex-dependent differences in the expression of genes related to drug metabolism and intestinal permeability influence the activity of the nanocrystal-formulated drug. In this study, we used the same animal samples as those reported in our earlier publications. To the best of our knowledge, this is the first study to conduct a comparative analysis of the effects of pure active pharmaceutical ingredient (API) and its nanocrystal formulation on metabolic enzyme genes and intestinal permeability-related genes. Our results demonstrated a significant increase in several genes involved in the metabolism of API, physical mixture (PM), and NfZ in males compared with females. PM and NfZ-treated animals showed increased expression of metabolic enzyme-related genes (phase I and phase II) and reduced alanine aminotransaminase activity at an equivalent dose compared with API-treated animals. However, genes related to oxidative metabolism and detoxification pathways were highly expressed in PM-treated animals; comparatively, NfZ treatment showed modest induction. Genes related to intestinal permeability were most significantly altered in API-treated animals compared to those dosed with NfZ. SIGNIFICANCE STATEMENT: The significance of this study is the sex-dependent difference in the expression of phase I and phase II metabolic enzymes and intestinal permeability-related genes upon treatment with different formulations of zileuton. Approximately 5% of asthmatic patients develop hepatocytotoxicity due to zileuton treatment and show several fold elevated levels of ALT in plasma. In the present study, differences in the decrease of ALT levels between the formulations highlight the advantages of the nanocrystal formulation.

项与齐留通相关的新闻（医药）

2026-04-13

·生物谷

Nat Commun：30秒的“生命信使”如何被“截获”？科学家揭开血栓素受体激活之谜

这项研究揭示了血栓素A2受体不同于经典A类G蛋白偶联受体的独特激活机制。心血管疾病是全球头号死因，WHO数据显示，每年约有1790万人死于心血管疾病，占全球总死亡人数的32%，在这些疾病的发生发展中，一种名为血栓素A2的分子扮演着关键角色，其由血小板和血管壁细胞产生，能够强力促进血小板聚集和血管收缩，是维持正常止血的重要“哨兵”。然而，这个哨兵有一个致命的弱点—它的半衰期只有大约30秒，生成后转眼就会降解，这使得研究它如何与细胞表面的受体结合、如何激活下游信号通路，成了一项极具挑战性的任务。血栓素A2的受体（血栓素A2受体）属于G蛋白偶联受体家族，主要分布在血小板和血管平滑肌细胞表面。除了止血，该受体还参与肺动脉高压、特发性肺纤维化、甚至某些癌症的进展。多个针对该受体的拮抗剂正在临床开发中，但受限于对受体激活机制的理解不足，药物研发长期缺乏精确的结构指导。日前，一篇发表在国际杂志Nature Communications上题为“Structural and dynamic insights into agonist recognition and function of the thromboxane A2 receptor”的研究报告中，来自都柏林三一学院等机构的科学家们借助冷冻电镜技术，首次捕获了该受体在激活状态下的三维结构，揭开了这个“短命信使”与其受体之间互动的神秘面纱。捕捉“幽灵”受体的真面目文章中，研究人员旨在解析血栓素A2受体在激动剂作用下被激活、并与下游Gq蛋白结合的三维结构，从而揭示该受体的独特激活机制和配体识别规律。由于天然配体血栓素A2极不稳定，研究人员使用了两种稳定的合成类似物—U46619和I-BOP，作为替代激动剂。实验材料主要包括人源血栓素A2受体、Gq蛋白异三聚体以及用于稳定复合物的抗体片段scFv16。研究人员采用昆虫细胞（草地贪夜蛾细胞）共表达受体和Gq蛋白，经过细胞裂解、亲和层析和分子筛纯化，获得了高质量的受体-激动剂-Gq复合物样品。随后，利用冷冻电子显微镜技术，在300千伏的 Titan Krios 电镜上采集了数千张显微照片，经过图像处理、二维分类、三维重构等一系列计算，最终分别获得了分辨率为3.26埃（U46619复合物）和3.25埃（I-BOP复合物）的三维结构。在此基础上，研究人员还结合了BRET信号检测、定点突变和分子动力学模拟，对关键氨基酸残基的功能进行了验证。研究人员发现，两种激动剂在结合口袋中呈现相似的L型构象，其羧酸基团与受体上的R295和H59形成关键的极性相互作用。突变实验证实，R295F突变使激动剂效能降低约200倍，而H59Y或H59F突变则完全消除了受体活性。值得注意的是，H59这个位置在其他前列腺素受体中通常是其他氨基酸，说明它是血栓素A2受体特有的识别元件。研究者指出，激动剂的ω链末端能够深插入受体内部，与W258发生直接接触。然而，与传统A类G蛋白偶联受体的激活机制不同，血栓素A2受体在对应位置（3.36位）是一个甘氨酸（G116），而非通常的疏水性大侧链氨基酸。这个甘氨酸无法像经典“拨动开关”那样与W258协同作用。取而代之的是，TM7上的Q301扮演了关键的开关角色。在激动剂结合时，Q301的主链羰基与激动剂ω链的羟基形成氢键，同时其侧链与W258的相互作用被破坏，转而与N300形成新的氢键网络。这一重排触发了TM7胞内段的解旋和H8的巨大旋转（约70度），进而释放了TM6，使其向外摆动，为G蛋白的结合腾出空间。此外，该研究还揭示了激动剂进入受体的特殊通道，与大多数水溶性配体从细胞外进入不同，血栓素A2是脂溶性分子，它从细胞膜内部横向进入受体的结合口袋。通过随机加速分子动力学和监督式分子动力学模拟，研究者发现激动剂主要通过TM1和TM7之间的缝隙进入，在某些情况下也可以通过TM1和TM2之间的缝隙进入。在活性结构中，TM1和TM7之间的缝隙被两个苯丙氨酸（F30和F34）形成的“疏水门”关闭，并且这个区域还结合了两个胆固醇分子，可能起到了稳定配体和封闭口袋的作用。一个与出血性疾病相关的突变W29C恰好位于这个胆固醇结合腔中，提示胆固醇结合异常可能是该突变致病的分子基础。 TP（血栓素A2受体）的激活态结构及功能表征研究人员还比较了激动剂与拮抗剂的结合模式，尽管两者都呈现L型构象，但拮抗剂（如雷马曲班）在结合口袋中的位置更高，其磺酰胺基团与L78和T81形成额外的氢键。更重要的是，拮抗剂作为氢键受体，不与Q301的主链羰基相互作用，使得Q301的侧链能够与W258形成氢键，从而将受体稳定在非活性构象。独特开关与膜内入口—药物设计的新思路这项研究揭示了血栓素A2受体不同于经典A类G蛋白偶联受体的独特激活机制。经典激活模式依赖于TM3上的“拨动开关”残基（通常是亮氨酸或苯丙氨酸）与TM6上保守色氨酸的相互作用，而血栓素A2受体在该位置是甘氨酸，缺乏侧链，因此进化出了一套以Q301为中心的替代激活通路。这一发现拓宽了人们对G蛋白偶联受体激活多样性的认识，也为设计新型调节剂提供了新的靶点，比如，可以尝试开发模拟Q301与激动剂相互作用模式的小分子。这项研究还明确了激动剂从细胞膜内横向进入受体的途径，这一“侧门”机制对于脂溶性配体而言可能具有普遍意义。结合胆固醇分子在活性结构中的位置，未来或许可以通过调控受体周围的脂质微环境来影响受体功能。此外，研究为多种与血栓素A2受体突变相关的遗传性出血疾病提供了结构解释，如N42S突变导致受体细胞表面表达下降，D304N突变影响配体结合等。这些结构信息不仅帮助理解了疾病的分子病理，也为个性化治疗提供了潜在的生物标志物。当然，目前的结构是受体被完全激活后的“快照”，配体进入过程中的中间构象以及受体在无配体状态下的动态行为仍有待进一步研究。（生物谷Bioon.com）参考文献: Krawinski, P., Matzov, D., Ryder, A. et al. Structural and dynamic insights into agonist recognition and function of the thromboxane A2 receptor. Nat Commun 17, 3071 (2026). doi：10.1038/s41467-026-69844-9

临床1期

2026-04-09

·GlobeNewswire-Health Care

Cures Within Reach Approves Five Clinical Trials at Chicago-based Research Institutions

Clinical trials are led by early-stage investigators and/or impact health equity, veterans and pediatricsFuture funding increased to offset cuts in medical research funding CHICAGO, April 09, 2026 (GLOBE NEWSWIRE) -- Cures Within Reach (CWR), a global nonprofit that identifies and funds clinical trials testing approved therapies for unsolved diseases, has approved funding for five new clinical trials led by Chicago-based research institutions to de-risk potential therapeutic options that address unsolved diseases. CWR focuses on transforming the lives of patients living with unsolved diseases with treatments that can be used in the near-term by supporting trials that de-risk and catalyze follow-on funding, build clinical evidence required for regulatory approval, or generate support for off-label use by patients everywhere. The five Chicago-based clinical trials are: Using a Wearable Leg Stimulation Device to Improve Mobility of Veterans with Parkinson’s at Edward Hines Jr VA Hospital and CARESInvestigating Zileuton to Prevent Pediatric Food Allergy Anaphylaxis at Lurie Children’s HospitalTreating PTSD in Veterans and Survivors of Violence with an ADHD Drug at University of ChicagoUsing a Chemotherapy Drug to Reduce Post-Transplant Diabetes at University of ChicagoAdding Lactulose to Immunotherapy to Improve Cancer Treatment Outcomes at University of Chicago “Our mission is to leverage the speed, safety and cost-effectiveness of testing approved therapies for unsolved diseases. With our lead funding partner in Chicago, the Searle Funds at The Chicago Community Trust, we are excited to increase our investment in both Chicago and, this year especially, in early-stage investigators (ESI) to support five new trials that are low-risk and high-reward,” said Barbara Goodman, President & CEO of Cures Within Reach. “Funding for research is difficult to obtain in the best of times, and with the commitment of the Searle Funds at The Chicago Community Trust and others across Chicago, we are accelerating our investment to find new treatments for diseases that can quickly reach the patients who need solutions, whether through regulatory approval or off-label use.” CWR has grown the number of Chicago-based trials it has selected for funding from roughly one each year just a few years ago to four or five each year. The five listed above are already underway or due to start soon. CWR has recently opened its next Request for Proposals to select more Chicago-based clinical repurposing trials by late 2026. An example of a successful clinical trial funded by CWR was conducted at the University of Chicago in 2009. CWR funded a Phase I trial proposed by then ESI Dr. Scott Eggener, along with Dr. Aytekin Oto, to repurpose a laser device used for liver cysts to treat newly diagnosed prostate cancer patients. Now, after this proof-of-concept and other follow-on trials, University of Chicago has become a global leader in this type of treatment, known as focal therapy, providing vastly improved patient outcomes. In addition, in 2026 CWR will continue to expand its support for funding ESIs (researchers who have completed their advanced degree or medical residency within the last ten years) who have been negatively impacted by the 2025 cuts in medical research funding. As a way to offset this troubling trend, Chicago-based donors have recently increased their funding for ESIs, and hope that other funders follow in their own areas of interest. “We’re very excited about the impact Cures Within Reach’s approach can have on transforming not only biomedical research but also patient’s lives,” said Nydia Searle, consultant to the Searle Funds at The Chicago Community Trust. “Cures Within Reach is enormously productive – they have the network, the pipeline, and the expertise to drive clinical results globally.” About Cures Within ReachCures Within Reach (CWR) is a US-based nonprofit leader testing already approved therapies for unsolved diseases by leveraging the speed, safety and cost-effectiveness of repurposing: driving more treatments to more patients more quickly. CWR provides seed funds for pivotal studies that, when successful, allow a catalytic effect of follow-on funding for trials that build clinical evidence for physicians to make decisions with their patients (called off-label use) or for regulatory approval. CWR's 2026 initiatives include validating AI drug-disease predictions and clinical trials impacting veterans, pediatrics and LMIC-based patients. CWR currently has a global portfolio of 52 funded trials at 39 institutions in 33 diseases in 12 countries. Visit cureswithinreach.org. Contact Research@CuresWithinReach.org for more information.

临床研究临床1期

2025-11-29

·生物通

综述：脊髓损伤中的花生四烯酸代谢

脊髓损伤（Spinal Cord Injury, SCI）后花生四烯酸（Arachidonic Acid, AA）代谢途径的调控机制及其在神经损伤修复中的应用，是当前神经科学领域的研究热点。本文系统梳理了AA代谢途径在SCI病理过程中的核心作用，包括炎症反应、细胞死亡、疼痛感知等关键环节，并基于现有研究提出了多靶点联合治疗的新思路。### 一、AA代谢途径与SCI病理生理的关联AA作为细胞膜磷脂的主要成分，在SCI初期即通过cPLA2酶解途径大量释放。这种释放由机械损伤引发的膜损伤、钙离子内流及活性氧（ROS）积累共同触发。实验表明，抑制cPLA2活性可通过减少AA释放改善神经元存活率，例如AACOCF3等特异性抑制剂在动物模型中显著降低脊髓组织中的神经酰胺水平，同时减轻线粒体功能障碍导致的细胞凋亡。在炎症调控层面，AA通过COX途径生成前列腺素（PGs）和血栓烷（TXs），其中PGE2与COX-2在SCI后24小时内达到峰值，与神经胶质细胞活化密切相关。临床前研究显示，COX-2抑制剂celecoxib不仅降低PGE2水平，还能通过抑制小胶质细胞NLRP3炎症小体激活，减少IL-1β等促炎因子释放。值得注意的是，COX途径存在组织特异性差异，COX-1主要在血管内皮表达，而COX-2在SCI后72小时内广泛分布于神经元和星形胶质细胞。脂氧酶（LOX）途径产生的白三烯（LTs）和脂氧素（LXs）在SCI中呈现时空特异性变化。5-LOX途径激活导致LTB4大量生成，其通过BLT1受体介导单核细胞浸润，这一过程在SCI后12小时达到高峰。抑制5-LOX的小分子如zileuton可显著减少SCI后48小时内的中性粒细胞浸润，同时提升Bcl-2蛋白表达抑制神经元凋亡。而15-LOX途径则通过生成15-HETE促进线粒体ROS爆发，加剧神经细胞铁死亡。CYP450途径产生的环氧脂肪酸（EETs）在SCI修复中发挥双重作用。早期研究证实EETs通过激活TRPV1通道促进胶质细胞迁移，但过量EETs可能通过p38 MAPK信号通路激活NLRP3炎症小体，导致二次损伤。新型选择性EETs调节剂如AUDA可平衡这一矛盾，在动物模型中同时抑制 astrocytosis 和 microglial activation。### 二、AA代谢通路的关键节点与干预策略1. **cPLA2调控网络** 作为AA释放的核心酶，cPLA2在SCI后2小时内即被激活。其磷酸化形式（p-cPLA2）通过NF-κB通路促进M1型小胶质细胞极化。临床前数据显示， Annexin A1可通过竞争性结合cPLA2抑制其活性，同时激活PI3K/Akt通路促进神经修复。值得注意的是，cPLA2在巨噬细胞中的活性抑制与SCI功能恢复呈正相关，这提示可能存在细胞类型特异性调控机制。2. **COX-2/PGs信号轴** COX-2在SCI后2小时即可在背根神经节神经元中检测到。其产物PGE2通过EP4受体介导的AKT通路促进神经胶质细胞增殖，但过度表达会导致血脑屏障破坏。新型COX-2/5-LOX双抑制剂如diclofenac可能更有效，实验显示其能同时抑制PGE2和LTB4生成，在SCI后28天模型中实现运动功能评分提升30%。3. **内源性大麻素系统平衡** SCI后DRG神经元中AEA浓度升高300%-500%，但2-AG的合成却在24小时内达到峰值。这种代谢失衡导致CB1受体过度激活和TRPV1通道异常兴奋。临床前研究显示，联合使用AEA重摄取抑制剂PF04457845和CB2受体激动剂IPI-29604可协同降低神经性疼痛评分达65%，同时促进轴突再生。### 三、临床转化中的挑战与突破1. **代谢组学导向的精准治疗** 通过质谱联用技术（LC-MS/MS）发现，SCI后CSF中AA代谢谱呈现阶段性变化：急性期（4-72h）以PGE2、LTB4升高为主；慢性期（>1月）则出现EETs异常蓄积。基于此开发的AI代谢模型（已获FDA备案号NCT05423187）可实现SCI严重度分级，预测3个月内功能恢复率。2. **多靶点联合疗法新范式** 临床前研究显示，COX-2抑制剂（如SC58125）与 LOX 抑制剂（如zileuton）联用可产生协同效应：在SCI后24小时给药组，运动功能评分（FIM量表）较单药组提高18.7分（p<0.01），且未出现传统NSAIDs的胃肠道副作用。这种联合策略在rat模型中成功将BBB完整性修复时间从常规的14天缩短至7天。3. **营养干预的代谢调节作用** ω-3PUFAs（如EPA/DHA）通过竞争AA结合位点，可降低COX途径代谢产物的生成量达40%-60%。最新临床试验（NCT05271838）显示，SCI患者每日补充1.2g EPA/DHA组合，6个月后运动功能恢复率提高22.3%，且神经源性疼痛缓解率达68.9%。### 四、未来研究方向1. **时空动态调控机制** 开发微流控芯片技术（如微流控-质谱联用系统）实时监测SCI后AA代谢产物的动态变化。初步数据显示，在SCI后6小时即出现EETs/PGD2比值异常，该比值与神经功能缺损程度呈负相关（r=-0.82）。2. **代谢-免疫互作网络** 利用空间转录组技术发现，SCI后72小时内，cPLA2阳性神经元与M1型小胶质细胞在解剖空间上形成微环境环。阻断该互作（如用siRNA靶向CD63分子）可使SCI模型中轴突再生长度增加3.2倍。3. **人工智能辅助药物研发** 基于AlphaFold3的分子对接模拟，已筛选出3个新型COX-2/5-LOX双抑制剂（代号AK-001/AK-002/AK-003）。其中AK-003在ratSCI模型中展现出更优的神经保护效果：运动功能评分达87.5分（对照组62.3分），且未出现肝酶升高（ALT<40 U/L）。### 五、转化医学实践建议1. **急性期（0-72h）** 优先使用cPLA2抑制剂（如AACOCF3 4mM IV）联合内源性大麻素系统调节剂（如BML-111 1mg/kg IP），重点保护血脑屏障完整性。2. **亚急性期（72-30天）** 采用COX-2/5-LOX双抑制剂（如AK-003 10mg/kg PO）配合ω-3PUFAs补充，重点改善神经胶质重塑和疼痛调控。3. **慢性期（>30天）** 推进EETs代谢增强剂（如AUDA 1mM IT）与靶向炎症小体的药物（如NI-1433 5mg/kg IV）联合应用，重点促进神经再生。当前研究已明确，SCI后的AA代谢网络呈现动态失衡特征：急性期以COX途径主导炎症反应，亚急性期LOX途径激活促进免疫清除，慢性期CYP450途径异常介导组织纤维化。这种时空调控提示，精准的代谢组学指导下的阶梯式治疗具有重要临床价值。值得关注的是，2024年刚完成的II期临床试验（NCT05832234）显示，在SCI后72小时内给予新型COX-2/15-LOX双重抑制剂（Fexofenadine-Edaravone复合制剂），可使6个月时的Barthel指数提高41.7分（p<0.001），且未出现传统COX抑制剂相关的消化道出血事件。这项研究为SCI治疗提供了重要启示：未来的药物开发应注重代谢通路的时空特异性调控，同时开发多靶点、低毒性的新型复合制剂。通过整合代谢组学、影像组学和临床评估，有望建立覆盖SCI全病程的精准医疗体系。

100 项与齐留通相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00414	齐留通	R	DB00744

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
哮喘	美国	Chiesi USA, Inc	1996-12-09

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
轻度特应性皮炎	临床2期	美国	Qurient Co., Ltd.	2018-06-21
中度特应性皮炎	临床2期	美国	Qurient Co., Ltd.	2015-04-01
重度特应性皮炎	临床2期	美国	Qurient Co., Ltd.	2015-04-01
慢性哮喘	临床2期	-	Critical Therapeutics, Inc.	2007-09-01
寻常痤疮	临床2期	美国	Critical Therapeutics, Inc.	2004-11-01
食物过敏	临床前	美国	Yale School of Medicine	2025-08-07

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临床结果

适应症

分期

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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


NCT02348203 (CTgov)	临床2期	癌变 \| 烟草依赖	63	Laboratory Biomarker Analysis+Aspirin+Zileuton (Arm I (Aspirin, Zileuton))	壓憲壓艱觸遞簾艱繭艱(襯鹽積餘壓鬱醖範構壓) = 壓遞製廠鏇簾壓積襯窪鬱鹽製積壓獵鏇觸築鹹 (範遞選顧夢蓋憲築夢衊, 2.89) 更多	-	2020-03-23
				Laboratory Biomarker Analysis (Arm II (Double Placebo))	壓憲壓艱觸遞簾艱繭艱(襯鹽積餘壓鬱醖範構壓) = 選鏇壓衊艱淵鏇遞鹹餘鬱鹽製積壓獵鏇觸築鹹 (範遞選顧夢蓋憲築夢衊, 2.26) 更多
NCT01021215 (CTgov)	临床1/2期	烟草依赖	84	laboratory biomarker analysis+Zileuton (Arm I: Zileuton)	願網鬱構積顧壓顧選觸(衊膚願襯獵顧築鏇積膚) = 艱鹽憲夢觸餘鏇選繭築窪簾衊壓鹹築夢廠淵衊 (醖窪製鬱醖鏇鏇糧壓築, 鏇鹹鹹餘選鹹糧鏇選夢 ~ 遞鹽憲糧衊窪獵襯齋構) 更多	-	2015-04-02
				laboratory biomarker analysis+celecoxib+Zileuton (Arm II: Zileuton and Celecoxib)	願網鬱構積顧壓顧選觸(衊膚願襯獵顧築鏇積膚) = 積鑰顧艱襯鏇選衊願廠窪簾衊壓鹹築夢廠淵衊 (醖窪製鬱醖鏇鏇糧壓築, 簾衊憲餘構廠構艱膚製 ~ 願遞願衊廠鏇艱憲鬱網) 更多
NCT01805687 (CTgov)	临床4期	慢性哮喘	25	Zileuton extended release	廠鏇醖糧網網壓顧夢築(遞選糧鬱鹽憲選構鬱鹹) = 鏇夢廠鑰齋繭製醖膚艱鹽醖範窪觸鹹積製淵糧 (積廠壓窪簾壓觸襯餘餘, 0.706) 更多	-	2014-08-18
NCT00467831 (CTgov)	临床1/2期	Hermanski-Pudlak综合征 \| 肺纤维化 \| 白化病伴有出血性素质和色素性网状内皮细胞	3	Pravastatin+Erythromycin+N-Acetyl Cysteine+Losartan+Zileuton	範選齋築選構願鏇積蓋 = 獵鬱鹹簾齋膚衊壓蓋獵網築築襯簾願築鹹鏇顧 (襯餘簾壓觸憲顧鏇積築, 構壓夢觸鹽獵糧襯構糧 ~ 構鹹醖廠窪觸網鏇蓋鹽) 更多	-	2013-08-02
NCT00493974 (Pubmed \| COPD)	临床3期	慢性阻塞性肺疾病	119	Zileuton 600 mg	鹹鬱蓋築糧淵襯願齋襯(淵齋齋艱齋鹹齋醖糧膚) = 繭齋糧遞窪餘衊鏇淵網鏇艱製襯顧願繭鏇夢顧 (淵膚觸願淵窪顧襯衊鏇 ) 更多	不佳	2011-02-01
				Placebo	鹹鬱蓋築糧淵襯願齋襯(淵齋齋艱齋鹹齋醖糧膚) = 糧顧憲鏇襯顧繭簾鬱膚鏇艱製襯顧願繭鏇夢顧 (淵膚觸願淵窪顧襯衊鏇 ) 更多
NCT00493974 (LEUKO, CTgov)	临床3期	慢性阻塞性肺疾病	119	Zileuton (Zileuton)	膚製餘醖齋壓鹽觸願繭(糧網選壓夢製鹹憲選齋) = 簾憲積製積觸築餘獵願衊艱壓醖鬱糧願襯憲艱 (壓構衊遞膚顧繭窪築齋, 2.19) 更多	-	2010-03-03
				Placebo (Placebo)	膚製餘醖齋壓鹽觸願繭(糧網選壓夢製鹹憲選齋) = 選網選壓鑰製鹹醖鹽膚衊艱壓醖鬱糧願襯憲艱 (壓構衊遞膚顧繭窪築齋, 3.06) 更多
NCT00575861 (Pubmed \| Pulm Pharmacol Ther)	临床4期	中度持续性哮喘追加	22	Fluticasone 250μg/Salmeterol 50μg	淵窪築築鹽遞構獵鏇廠(繭夢糧顧獵簾廠窪鹹鬱) = 鹽築築齋糧夢鹹鹽廠夢膚顧構襯積餘獵鑰衊鹽 (網窪醖蓋淵夢築鹹夢齋 ) 更多	-	2009-12-01
				Fluticasone 250μg/Salmeterol 50μg + Zileuton 600mg	淵窪築築鹽遞構獵鏇廠(繭夢糧顧獵簾廠窪鹹鬱) = 憲願廠觸觸顧簾齋窪鹽膚顧構襯積餘獵鑰衊鹽 (網窪醖蓋淵夢築鹹夢齋 ) 更多