A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of the NOX1/4 Inhibitor Setanaxib in Patients With Alport Syndrome

The purpose of the study is to learn about the safety and tolerability of setanaxib in subjects with Alport syndrome, when added to their standard of care treatment. The study will assess how safe setanaxib is when compared to placebo. Study participants will be asked if they are experiencing any side effects at each study visit. In addition, tests in blood, urine and other examinations will be used to look at the safety of setanaxib. The study will also measure how well setanaxib works in comparison to a placebo, by measuring urine protein and certain markers in the blood and urine. The concentration of setanaxib in the blood will also be measured throughout the course of the study.
Setanaxib is planned for use together with the current standard of care to hopefully provide additional therapeutic benefits by preserving kidney function.
The study will be conducted at multiple research sites in the UK, Spain, and Czech Republic. Eligible participants will be randomly assigned to receive either setanaxib or placebo. Setanaxib dose level will depend on age and all participants will receive their standard of care in addition to setanaxib or placebo. The study consists of a Screening period of up to 4 weeks, a 24-week Treatment period and a 4- week Follow-up period.

开始日期2023-11-27

申办/合作机构

Calliditas Therapeutics AB

NCT05323656

/ Completed临床2期

A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Setanaxib, When Administered With Pembrolizumab, in Patients With Recurrent or Metastatic SCCHN

The primary objective of this study is to compare the change in tumour size per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in recurrent or metastatic SCCHN patients treated with setanaxib and pembrolizumab versus patients treated with placebo and pembrolizumab.

开始日期2022-04-06

申办/合作机构-

NCT05014672

/ Completed临床2期

TRANSFORM: A 24-week, Randomized, Placebo-controlled, Double-blind, Phase 2b Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Elevated Liver Stiffness

The primary objective of this study is to evaluate the effect of setanaxib on alkaline phosphatase (ALP) at Week 24 in participants with PBC and with elevated liver stiffness and intolerance or inadequate response to ursodeoxycholic acid (UDCA).

开始日期2022-02-14

申办/合作机构-

100 项与 Setanaxib 相关的临床结果

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100 项与 Setanaxib 相关的转化医学

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100 项与 Setanaxib 相关的专利（医药）

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156

项与 Setanaxib 相关的文献（医药）

2026-03-01·PEDIATRIC NEPHROLOGY

From RAAS blockade to regenerative medicine: evolving treatment strategies in Alport syndrome

Review

作者: Kim, Jin-Ju ; Lo Re, Claudia ; Fornoni, Alessia

Abstract:

Alport syndrome (AS) is a hereditary glomerulopathy caused by mutations in the COL4A3 , COL4A4 , or COL4A5 genes, leading to progressive kidney decline and extrarenal manifestations. Advances in genetic testing have enabled the reclassification of AS into X-linked, autosomal recessive, and autosomal dominant forms, facilitating more accurate diagnosis and risk stratification. While renin-angiotensin-aldosterone system (RAAS) blockade remains the foundation of treatment to delay kidney failure, it does not directly target the underlying molecular pathology. Adjunctive commercially available metabolic modulators, including SGLT2i, mineralocorticoid receptor antagonists, ezetimibe and GLP-1 receptor agonists, may offer additional kidney protection. Ameliorating therapies being tested in Phase II trials include endothelin receptor antagonists (e.g., atrasentan), dual endothelin receptor antagonist and angiotensin II receptor inhibition (e.g., sparsentan) FXR agonists (e.g., vonafexor), inducers of cholesterol efflux (e.g., VAR200 and R3R01), and NOX1/4 inhibitors (e.g., setanaxib), several of which are currently being evaluated in clinical trials. Novel strategies such as exon skipping, gene editing, and nonsense mutation readthrough (e.g., ELX-02) are advancing toward precision medicine approaches as disease modifying agents targeting the genetic cause of AS. Moreover, therapies targeting mitochondrial function, such as mitophagy enhancers, have demonstrated preclinical promise. Stem cell-based approaches are also being explored for their regenerative and anti-fibrotic effects. This review summarizes the current landscape of AS classification and treatment, highlighting both standard interventions and experimental therapies. Emphasis is placed on the molecular mechanisms underlying podocyte injury and fibrosis, recent preclinical findings, and ongoing clinical trials that may shift future therapeutic paradigms. Graphical abstract

2026-01-01·EUROPEAN JOURNAL OF PHARMACOLOGY

Basal release of 6-cyanodopamine in human vas deferens, a new endogenous catecholamine that enhances smooth muscle contractility

Article

作者: Miller, Alex Henrique ; Jabbour, Sami ; De Nucci, Gilberto ; Fregonesi, Adriano ; Britto-Júnior, José ; Antunes, Edson ; Moraes, Maria Elisabete A ; Lima, Antonio Tiago ; Peterson, Larryn W ; Luvizotto, Rodrigo

6-Cyanodopamine (6-CYD) is a novel endogenous catecholamine that is released from rat isolated vas deferens epithelium and regulates smooth muscle contractility. Here it was investigated whether 6-CYD is released from human epididymal vas deferens (HEVD) and its interaction with the classical catecholamines dopamine, noradrenaline, and adrenaline. Basal release of 6-CYD was quantified by liquid chromatography coupled to tandem mass spectrometry in the absence and presence of either the voltage-gated sodium channel blocker tetrodotoxin or the dual NADPH oxidase NOX_1,4 inhibitor GKT137831. Concentration-response curves to dopamine, noradrenaline, and adrenaline were performed in the presence and absence of 6-CYD. Frequency-dependent electric-field stimulation (EFS) was conducted with and without pre-incubation with 6-CYD. The basal release of 6-CYD was decreased with pre-incubation with GKT137831 and unaffected by tetrodotoxin. Although 6-CYD itself (up to 100 μM) did not induce HEVD contractions, at 10 nM it remarkably potentiated the contractions induced by dopamine, noradrenaline, and EFS. At 100 nM, 6-CYD also potentiated the adrenaline-induced HEVD contractions. The potentiation of noradrenaline-induced contractions by 6-CYD was not observed in HEVD pre-treated with tetrodotoxin (1 μM). In separate experiments, HEVD strips also released 6-nitrodopamine (6-ND) that was significantly reduced by GKT137831 (1 μM). Co-incubation (30 min) with 6-CYD (100 pM) and 6-ND (100 pM) caused a significant leftward shift in the concentration-response curve to noradrenaline. The results indicate that epithelium 6-CYD is an endogenous mediator of HEVD contractility. Whether NADPH oxidases are involved in 6-CYD biosynthesis remains to be further investigated.

2026-01-01·PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY

Pyraclostrobin induces brain oxidative stress, apoptosis and inflammation through mitochondrial phosphorylation-induced ROS activation of the p38 MAPK pathway

Article

作者: Chen, Yaru ; Chen, Jingjing ; Dong, Zibo ; Zhao, Panpan ; Dong, Qian ; Li, Yuanyuan ; Jin, Xiaomin

Pyraclostrobin (PY), a widely used fungicide, poses potential neurotoxic risks to mammals.This study investigates the effects of PY on brain damage in mice, while also exploring the underlying mechanisms. This study demonstrates that PY induces neuronal damage in mouse brains. ELISA analysis revealed elevated levels of S100β and NSE in serum, as well as the expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α were increased, suggesting that PY can cause brain damage in mice. Biochemical assays further indicated a significant rise in MDA levels in brain tissue and BV-2 cell line treated with PY, accompanied by a marked decrease in antioxidant indicators such as CAT, T-AOC, and GSH, which implies that PY triggers oxidative stress. TUNEL fluorescence staining experiments, combined with the expression profiles of Cleaved-caspase-3, Bcl-2, Cleaved-caspase-8, Cleaved-caspase-9, Cytochrome c, and Bax, confirm that PY induces apoptosis in both mouse brains and BV-2 cells. QPCR results show that the anti-inflammatory factor il-10 is downregulated in brain tissue and BV-2 cell line treated with PY, indicating that PY promotes inflammation in these tissues. Moreover, Adezmapimod blocking experiments reveal that PY activates the MAPK signaling pathway, thereby promoting apoptosis, inflammation, and oxidative stress. NAC and GKT137831 blocked ROS-mediated MAPK signaling. JC-1 and DHE staining experiments further demonstrate that PY causes mitochondrial dysfunction in the mouse brain and significantly increases ROS production. Collectively, these findings enhance our understanding of the neurotoxic effects of PY pesticide residues and provide a scientific foundation management.

项与 Setanaxib 相关的新闻（医药）

2026-04-15

·SM4Life

从泛抑制到精准靶向：NOX亚型选择性抑制剂，慢性病治疗的下一个研发风口！

氧化应激是贯穿心血管疾病、神经退行性病变、器官纤维化、慢性炎症等数十种慢性病的核心病理机制。长期以来，人们普遍认为活性氧（ROS）只是细胞代谢的“有害副产物”，直到NADPH氧化酶（NOX）家族的发现，才揭开了ROS主动生成的关键机制，NOX是哺乳动物体内唯一以生成ROS为核心功能的酶家族，其异常激活是多种疾病发生发展的“始作俑者”。近年来，随着对NOX亚型功能的深入解析，亚型选择性NOX抑制剂已成为全球新药研发的热门赛道，为众多未被满足的临床需求带来了全新治疗希望。 NOX家族：生理功能与病理损伤的“双刃剑” 人类NOX家族包含7个亚型：NOX1-5、DUOX1与DUOX2，不同亚型的组织分布、激活机制和生理功能存在显著差异，共同维持机体氧化还原稳态。生理状态下，NOX家族介导生成的低浓度ROS，是宿主免疫防御、细胞信号传导、激素合成、组织分化与稳态维持的关键分子：比如NOX2主要表达于吞噬细胞，是机体抵御病原体入侵的核心防线；NOX4在血管、肾脏组织中高表达，参与血管稳态调节；DUOX1/2则在甲状腺、呼吸道黏膜中发挥激素合成与黏膜防御作用。但当NOX亚型异常过度激活时，会持续生成过量ROS，打破细胞氧化还原平衡，触发氧化应激、炎症级联反应、细胞凋亡与组织病理性重塑，成为疾病发生的核心推手。这一特性也让NOX家族成为横跨多系统疾病的关键治疗靶点。横跨多系统的疾病相关性，NOX成治疗核心靶点目前已有大量研究证实，NOX家族异常激活与多种疾病的进展密切相关，其致病作用具有明确的亚型特异性：心血管疾病：NOX1、NOX2、NOX4的过度激活，会驱动动脉粥样硬化、高血压、心肌梗死与心力衰竭的发生发展，是血管损伤与心肌重构的核心诱因；神经退行性疾病：小胶质细胞中NOX2、神经元中NOX4的激活，会加剧阿尔茨海默病、帕金森病、缺血性脑卒中的神经炎症与氧化损伤，是神经元死亡的重要机制；纤维化疾病：NOX4是器官纤维化的核心驱动亚型，其过度激活会促进成纤维细胞活化与细胞外基质沉积，在特发性肺纤维化、肝纤维化、糖尿病肾病的进展中发挥关键作用；炎症与自身免疫病：NOX1、NOX2的异常激活，会放大炎症反应，参与类风湿关节炎、炎症性肠病的发病过程；同时NOX家族也与多种肿瘤的增殖、侵袭与转移密切相关。 NOX抑制剂研发：从非选择性到亚型精准靶向的跨越基于NOX在疾病中的核心作用，NOX抑制剂的研发已历经数十年发展，整体可分为两个阶段。第一代是非选择性NOX泛抑制剂，代表化合物包括二亚苯基碘鎓（DPI）、夹竹桃麻素（apocynin）、VAS2870等。这类化合物可抑制所有NOX亚型的活性，在临床前研究中被广泛用作工具化合物，但由于缺乏亚型选择性，不仅会阻断病理状态的ROS生成，还会抑制NOX家族的正常生理功能，同时还会作用于其他黄素酶，存在严重的脱靶毒性，无法应用于临床治疗。随着对NOX亚型功能差异的深入认知，研发的核心方向转向亚型选择性NOX抑制剂。这类抑制剂可精准靶向特定致病亚型，在阻断病理损伤的同时，最大程度保留其他亚型的正常生理功能，大幅降低毒副作用，成为目前全球研发的核心焦点，已有多款候选药物进入临床阶段。亚型选择性NOX抑制剂：全球研发进展与核心管线 1. NOX1/4双选择性抑制剂 Setanaxib，（曾用名GKT137831）是目前全球研发进展最快的NOX抑制剂，也是首个进入III期临床的亚型选择性NOX抑制剂，由Calliditas Therapeutics开发，可高选择性靶向NOX1与NOX4，对其他亚型几乎无抑制作用。截至2026年3月，该药物针对原发性胆汁性胆管炎（PBC）的适应症已进入III期临床，针对遗传性肾炎（Alport综合征）的适应症处于II期临床阶段，并已获得FDA授予的快速通道资格与多个孤儿药资格认定。临床数据显示，Setanaxib可通过抑制NOX1/4，从源头阻断氧化应激与纤维化进程，在Alport综合征患者中可显著减轻蛋白尿、延缓肾功能下降，展现出改变疾病进程的潜力。 GKT136901（别名AK120765）是NOX靶向领域首个实现亚型精准区分的标杆性小分子抑制剂，也是目前全球机制研究中应用最广泛的NOX1/4双亚型选择性工具化合物，由Genkyotex公司开发，可高选择性靶向NOX1与NOX4，对NOX2及其他氧化相关酶类几乎无抑制作用，脱靶风险极低。该化合物已在糖尿病肾病、特发性肺纤维化、缺血性脑卒中、类风湿关节炎等多种疾病模型中完成系统药效验证，是NOX亚型病理功能研究的核心工具分子，为同靶点临床候选药物的开发奠定了关键药理学基础。临床前研究数据显示，GKT136901可通过选择性抑制NOX1/4，从源头阻断活性氧过量生成、氧化应激级联反应与组织纤维化进程，在多种慢性病模型中可显著减轻靶器官损伤、延缓疾病进展，首次验证了NOX1/4双亚型选择性抑制在慢性病治疗中的可行性与应用潜力。 2. NOX2选择性抑制剂 GSK2795039是全球首个实现体内活性验证的高选择性NOX2亚型小分子抑制剂，也是NOX靶点机制研究中具有里程碑意义的工具化合物，由全球制药巨头葛兰素史克（GSK）开发，可通过NADPH竞争性方式靶向抑制NOX2，对其他NOX亚型、黄嘌呤氧化酶、内皮型一氧化氮合酶等氧化相关酶类均无显著抑制作用，具备极高的亚型选择性与极低的脱靶风险。研究数据显示，GSK2795039可通过选择性抑制NOX2，从源头阻断病理状态下的ROS生成与炎症级联反应，在小鼠足爪炎症、急性胰腺炎、心肌梗死等多种疾病模型中，可完全消除激活态NOX2介导的ROS产生，显著降低血清淀粉酶水平、减轻心肌重构与组织氧化损伤，改善疾病相关核心病理指标，是首个在体内验证了NOX2抑制治疗潜力的小分子化合物，为NOX2靶向药物的临床转化奠定了核心的药理学基础。３．NOX2/MAOB双靶点抑制剂 MC4762是全球首个first-in-class双靶点共价NOX2/MAOB抑制剂，也是神经炎症与神经退行性疾病领域极具研发潜力的亚型选择性NOX抑制剂，由国际科研团队基于经典NOX抑制剂母核优化开发，可高选择性靶向NOX2与MAOB双靶点，对NOX1、NOX3、NOX4、NOX5等其他NOX亚型，以及MAOA几乎无抑制作用，具备精准的靶点选择性与显著的抗炎、神经保护活性。临床前研究数据显示，MC4762可通过共价结合模式精准阻断NOX2与MAOB的生物学活性，从源头双重抑制ROS生成与神经炎症级联反应，其对NOX2与MAOB的IC50分别低至0.155 μM与0.182 μM。在BV2小胶质细胞神经炎症模型中，该化合物可强效降低细胞内ROS水平，对iNOS、IL-1β、IL-6等关键促炎细胞因子的下调效果，显著优于单靶点抑制剂（雷沙吉兰、VAS2870）及两药联用方案，在帕金森病、阿尔茨海默病、多发性硬化等神经退行性疾病模型中，展现出延缓神经元损伤、改善疾病进程的潜力。４. 其他亚型选择性抑制剂５、部分NOX抑制剂专利挑战与未来展望目前，NOX抑制剂的研发仍面临诸多挑战：NOX家族亚型同源性较高，高选择性抑制剂的设计难度大；部分疾病的核心驱动亚型尚不明确，影响了临床转化效率；ROS的生理功能与病理作用的边界难以精准把控。随着结构生物学的发展，NOX各亚型的晶体结构被逐步解析，为高选择性抑制剂的理性设计提供了坚实基础。未来，基于亚型精准靶向的NOX抑制剂，有望在器官纤维化、心血管疾病、神经退行性疾病等领域实现治疗突破，为慢性病的精准治疗开辟全新赛道，让更多患者受益于靶向氧化应激的创新疗法。往期精选：１、2026 Q1双抗ADC/双载荷ADC多点突破，下一代ADC将重塑实体瘤治疗格局！２、隐形巨头突围！Mission Therapeutics凭DUBs核心技术，破解ALS、肾病等难治性疾病困局３、全球首个β-catenin凝聚体调节剂进入临床！Dewpoint Therapeutics将改写“难成药靶点”新药发现规则！４、从Antibody-Linker-Payload迭代发展，看TF-ADC到底哪家强？５、全球首个口服补体因子B（CFB）抑制剂Iptacopan及其Followers！

2026-03-30

·PRNewswire

Calliditas Therapeutics AB to Present Exploratory Biomarker and Post-Hoc NefIgArd Analyses at the World Congress of Nephrology

Calliditas will present new secondary, biomarker, and mechanistic analyses from the Phase 3 NefIgArd study at the 2026 World Congress of Nephrology. Data further support Nefecon's gut–targeted, disease–modifying mechanism of action in IgA nephropathy. Calliditas to present seven posters and sponsor a scientific symposium highlighting the evolving IgAN treatment paradigm. STOCKHOLM, March 30, 2026 /PRNewswire/ -- Calliditas Therapeutics AB, an Asahi Kasei company, announced today that new data from the Phase 3 NefIgArd study in patients with primary immunoglobulin A nephropathy (IgAN) will be presented at the 2026 World Congress of Nephrology (WCN), taking place from March 28 to 31 in Yokohama, Japan. Nefecon's approval status, labeled indication, and availability vary globally. It is approved in the United States where it is marketed as TARPEYO® (budesonide) delayed-release capsules. It is available in Europe where it is marketed as Kinpeygo® by STADA Arzneimittel AG and in select countries in Asia, including Mainland China, Hong Kong, Macau, Taiwan, Singapore, and South Korea by Everest Medicines. It is also the subject of clinical trials in Japan by Viatris Pharamaceticals Japan Inc. The presentations will highlight secondary analyses from the Phase 3 NefIgArd study evaluating Nefecon, its effects on serum biomarkers associated with gut-associated lymphoid tissue (GALT) activity and the immunological impact of orally administered budesonide on B- and T-cell subsets in murine Peyer's patches following in vivo stimulation. These findings reinforce observations from earlier exploratory biomarker analyses and demonstrate the immunomodulatory effects in the Peyer's patches that underlie Nefecon's mechanism of action in modulating the mucosal immune system in the gut. Collectively, these data support a disease-modifying role for Nefecon in reducing levels of pathogenic galactose-deficient IgA1 in patients with IgAN. In total, 7 abstracts, of which 3 are based on secondary clinical efficacy and safety analyses from the Phase 3 NefIgArd study and 2 on mechanistic/biomarker analyses, will be presented. In addition, the initial demographics of the real-world PERFORM registry will be presented. Calliditas will also sponsor a symposium for educational scientific exchange, highlighting the evolving treatment paradigm in IgA nephropathy. Symposium and Presentation details as follows: Company Sponsored Symposium: Title: "The Evolving IgAN Treatment Paradigm: Why Target the Gut?" Date and time: March 30, 12:50 pm to 13:50 pm JST Presenters: Dr. Yusuke Suzuki, Juntendo University, Tokyo, Japan Dr. Sayna Norouzi, Loma Linda University Medical Center, Loma Linda, California, USA Dr. Chee Kay Cheung, University of Leicester, Leicester, UK Poster Presentations: Abstract No. WCN26-AB-8040 Title: "Impact of treatment with Nefecon on serum biomarkers of gut-associated lymphoid tissue function in patients with immunoglobulin A nephropathy from the Phase 3 NefIgArd trial" Date and time: March 30, 17:00 pm – 18:00 pm JST Presenter: Nadia Nawaz, College of Life Sciences, University of Leicester, Leicester, United Kingdom Abstract No. WCN26-AB-8197 Title: "Budesonide Modulates B- and T-Cell Immunity in Peyer's Patches: Implications for IgA Nephropathy" Date and time: March 28, 17:30 pm – 18:30 pm JST Presenter: Roza Ghotbi, Calliditas Therapeutics AB, Stockholm, Sweden Encore Poster Presentations: Title: "Urine protein–creatinine ratio response at 12 months in patients with immunoglobulin A nephropathy receiving Nefecon vs placebo: Analysis of NefIgArd trial data" Date and time: March 28, 17:30 pm – 18:30 pm JST Presenter: Richard Lafayette, Stanford University, CA Title: "Duration of absolute proteinuria response with Nefecon in patients with primary immunoglobulin A nephropathy: Results from the 2-year NefIgArd trial" Date and time: March 30, 17:00 pm – 18:00 pm JST Presenter: Brad Rovin , The Ohio State University Wexner Medical Center Title: "Absolute proteinuria over time with Nefecon vs placebo in patients with immunoglobulin A nephropathy: Results from the Phase 3 NefIgArd trial" Date and time: March 30, 17:00 pm – 18:00 pm JST Presenter: Heather Reich, University of Toronto Title: "The creation and initial demographics of the PERFORM™ Patient Registry: A novel real-world registry of patients treated for IgA nephropathy in the United States" Date and time: March 29, 17:00 pm – 18:00 pm JST Presenter: Russell Jones, Calliditas Therapeutics AB, Stockholm, Sweden Title: "Safety and preliminary efficacy findings from a Phase 2a randomized, double-blind, placebo-controlled trial of setanaxib in patients with Alport syndrome" Date and time: March 28, 17:30 pm – 18:30 pm JST Presenter: Daniel Gale , University College London The World Congress of Nephrology (WCN) is the flagship scientific, educational, and networking event of the International Society of Nephrology (ISN). Each year, WCN brings together kidney care professionals from around the world to exchange knowledge, showcase groundbreaking research, and participate in regionally-relevant symposia, training programs, and courses. About TARPEYO ® /Kinpeygo® TARPEYO is an oral 4mg delayed-release formulation of budesonide, designed to dissolve in the pH of the distal ileum. Each capsule contains coated beads of budesonide that target mucosal B-cells present in the ileum, including the Peyer's patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-IgA1), causing IgA nephropathy. About Primary Immunoglobulin A Nephropathy Primary immunoglobulin A nephropathy (IgA nephropathy or IgAN or Berger's Disease) is a rare, progressive, chronic immune-mediated disease that attacks the kidneys and occurs when galactose-deficient IgA1 is recognized by autoantibodies, creating IgA1 containing immune complexes that become deposited in the glomerular mesangium of the kidney. This deposition in the kidney can lead to progressive kidney damage, potentially resulting in end-stage kidney disease. IgAN most often develops between late teens and late 30s. IMPORTANT SAFETY INFORMATION FOR US AUDIENCE INDICATION TARPEYO is indicated to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis, have occurred with other budesonide formulations. WARNINGS AND PRECAUTIONS Hypercorticism and adrenal axis suppression: When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. When discontinuing therapy or switching between corticosteroids, monitor for signs of adrenal axis suppression. Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B). Immunosuppression and Increased Risk of Infection: Corticosteroids, including TARPEYO, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: reduce resistance to new infections, exacerbate existing infections, increase the risk of disseminated infections, increase the risk of reactivation or exacerbation of latent infections, and mask some signs of infection. Corticosteroid-associated infections can sometimes be serious. Monitor for infection and consider TARPEYO withdrawal as needed. Avoid corticosteroid therapy, including TARPEYO, in patients with active or quiescent tuberculosis or hepatitis B infection; untreated fungal, bacterial, systemic viral, or parasitic infections; ocular herpes simplex; or Kaposi's sarcoma. Avoid exposure to active, easily-transmitted infections (e.g., chickenpox, measles). Corticosteroid therapy may decrease the immune response to some vaccines. Other corticosteroid effects: TARPEYO is a systemically available corticosteroid and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where corticosteroids may have unwanted effects. ADVERSE REACTIONS In clinical studies, the most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO treated patients, and ≥2% higher than placebo) were peripheral edema (17%), hypertension (12%), muscle spasms (12%), acne (11%), headache (10%), upper respiratory tract infection (8%), face edema (8%), weight increased (7%), dyspepsia (7%), dermatitis (6%), arthralgia (6%), and white blood cell count increased (6%). DRUG INTERACTIONS Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine. Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide. USE IN SPECIFIC POPULATIONS Pregnancy: The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgAN. Infants exposed to in-utero corticosteroids, including budesonide, are at risk for hypoadrenalism. Please see Full Prescribing Information About Calliditas Therapeutics Calliditas Therapeutics is a biopharma company with offices in Stockholm, Sweden, focused on identifying, developing, and commercializing novel treatments in orphan indications with significant unmet medical needs. Visit Calliditas.com for further information. About Asahi Kase i Asahi Kasei is a diversified global company that contributes to life and living for people around the world. Since its foundation in 1922, with businesses in ammonia and cellulose fiber, Asahi Kasei has consistently grown through proactive portfolio transformation to meet the evolving needs of every age. With 50,000 employees worldwide, the company contributes to sustainability by providing solutions to the world's challenges across its three business sectors: Healthcare, Homes, and Material. For more information, visit . SOURCE Calliditas Therapeutics 21% more press release views with Request a Demo

临床3期上市批准临床结果临床2期

2026-03-16

·泰吉源直通车

控糖难防心脑梗，背后刺客是元凶：论走向C位的炎症/氧化应激

“医生，我血糖控制得很好，血脂也正常，血压也不高，为什么还是心梗了？” 这是内分泌科和心内科医生最常听到的疑问之一，也是最令人痛心的问题。数据显示，糖尿病患者发生心脑血管疾病的风险，是非糖尿病患者的2-3倍。即便严格遵循医嘱，将血糖、血脂、血压这“三驾马车”牢牢控制在理想范围，仍有近三分之二的糖尿病患者最终死于心血管并发症。为什么？因为在我们全力围堵高血糖这个“明面刺客”时，有两个更隐蔽、更凶狠的“背后元凶”从半路杀出——慢性炎症与氧化应激。它们长期被忽视，却恰恰是推动动脉粥样硬化进程的核心推手。而如今，随着国际学术界对糖尿病血管并发症机制的深入解析，这两个“刺客”终于被推到了聚光灯下，走向治疗策略的C位。一、明枪易躲，暗箭难防：“三控”为何拦不住血管危机？现行的糖尿病治疗策略，核心逻辑是“控制风险因素”：降糖药物把血糖降下来，他汀类药物把血脂压下去，降压药把血压稳住。这套“围点打援”的策略在过去几十年挽救了无数生命，功不可没。然而，这套策略存在一个根本性的盲区：它只处理了“源头”，却没有阻断“伤害的传导通路”。打个比方：高血糖就像是一个不断往血管里倾倒糖浆的工厂，而“三控”治疗只是在努力控制糖浆的倾倒速度。但问题是，即使你把糖浆倒得慢一点，那些已经流出来的糖浆，早已和血管壁上的蛋白质发生反应，生成了大量有害物质——晚期糖基化终末产物（AGEs）。 AGEs不是安静的“旁观者”，它们是真正的纵火犯。它们一旦形成，就会激活血管内皮细胞上的RAGE受体，然后同时点燃两把火：第一把火：炎症——AGEs激活免疫细胞，让它们持续释放炎症因子，血管壁变成“战场”。第二把火：氧化应激——AGEs激活NADPH氧化酶（尤其是NOX1和NOX5），大量产生活性氧，血管壁开始“生锈”。这两把火相互助燃：炎症促进氧化，氧化加剧炎症。最终的结果是：血管内皮受损，泡沫细胞形成，动脉粥样硬化斑块加速生长、变得不稳定。而这一切，即使血糖已经控制到正常范围，也可能仍在持续发生。这就是为什么，严格“三控”的患者，依然逃不过心梗和脑卒中——因为明枪易躲，暗箭难防。二、半路杀出的“程咬金”：炎症与氧化应激为何如此凶悍？如果说高血糖是幕后主使，那么炎症和氧化应激就是它雇来的两个“职业杀手”。它们的特点是什么？隐蔽、持久、破坏力强。而这恰恰是它们能够长期“隐身”、逃脱传统治疗围剿的原因。 1. 隐蔽性：悄无声息的血管风暴传统检测指标——血糖、血脂、血压——无法反映体内的炎症和氧化应激水平。很多患者拿到化验单，看到血糖达标、血脂正常，就以为“万事大吉”，殊不知血管深处早已暗流涌动。C反应蛋白、IL-6、氧化应激标志物这些真正反映“战况”的指标，却很少被纳入常规检测。 2. 持久性：挥之不去的“代谢记忆” AGEs一旦形成，半衰期很长，难以清除。更可怕的是，高糖环境会诱导免疫细胞形成一种 “代谢记忆”——即使血糖恢复正常，这些细胞仍然保持着“战斗状态”，持续释放炎症因子。这就是所谓的 “训练免疫” ，它让慢性炎症成为糖尿病患者的“标配”。一篇发表于《Circulation》的研究表明，将糖尿病小鼠的骨髓移植到非糖尿病小鼠体内，受体小鼠的动脉粥样硬化程度显著加重。这说明什么？免疫细胞已经“记住了”高糖环境，即使换了新环境，它们依然在搞破坏。 3. 破坏力：从斑块形成到斑块破裂炎症和氧化应激联手，几乎参与了动脉粥样硬化从起始到破裂的每一个环节： - 起始阶段：氧化应激氧化LDL，形成氧化型LDL，被巨噬细胞吞噬后形成泡沫细胞 - 进展阶段：炎症因子诱导血管平滑肌增殖、迁移，斑块逐渐增大 - 终末阶段：炎症因子降解斑块纤维帽的胶原蛋白，让斑块变得脆弱易破一旦斑块破裂，就是心梗、脑卒中——一锤定音的致命一击。三、走向C位：国际前沿如何擒住这两个“刺客”？面对这两个长期被忽视的“程咬金”，医学界并非束手无策。近年来，随着对糖尿病动脉粥样硬化机制的深入解析，一系列基于新机制的疗法正在从实验室走向临床。它们的目标非常明确：阻断高糖-AGEs-炎症/氧化应激-AS进展的恶性循环，补齐传统“三控”留下的最后一块短板。 1. 靶向AGEs及其受体：掐灭纵火犯的火柴既然AGEs是点燃两把火的“火柴”，那么阻止它点燃就是关键。RAGE拮抗剂的研发正在推进，试图从源头上切断AGEs的破坏信号。虽然目前尚无药物获批上市，但这一方向被认为是“擒贼擒王”的根本之策。 2. 靶向NADPH氧化酶：熄灭“氧化之火” 针对氧化应激的源头——NADPH氧化酶，新型抑制剂Setanaxib（靶向NOX1/NOX4）已进入临床试验。它的精妙之处在于：精准抑制有害的NOX1，同时保留保护性的NOX4，相当于“只抓坏人，不伤好人”。临床前研究显示，它在糖尿病动脉粥样硬化模型中同时提供肾脏和血管保护。更有意思的是NOX5——这个人类特有、小鼠没有的氧化酶亚型，在糖尿病和炎症条件下显著上调，与血管损伤密切相关。靶向NOX5的药物研发，正在成为新的热点。 3. 靶向炎症小体：浇灭“炎症之火” NLRP3炎症小体是连接代谢紊乱和血管炎症的关键枢纽。秋水仙碱——这个古老的治疗痛风药物，因能抑制NLRP3，意外成为心血管保护新星。COLCOT和LoDoCo2两项临床试验证实，秋水仙碱可显著降低心肌梗死患者的心血管事件风险。2023年，它正式获得FDA批准用于动脉粥样硬化治疗。而靶向IL-6的单抗Ziltivekimab，在慢性肾病伴炎症患者中展现出比现有抗炎药物更强的效果。RESCUE二期试验显示，它显著降低多种炎症和血栓形成标志物。目前，以心血管结局为终点的ZEUS三期试验正在进行中，结果令人期待。 4. 表观遗传调控：改写免疫细胞的“炎症记忆” 针对高糖诱导的“训练免疫”，BET蛋白抑制剂Apabetalone应运而生。它是首个获FDA突破性疗法认定的表观遗传药物，专门用于2型糖尿病患者的心血管二级预防。它的独特之处在于：能够“擦除”免疫细胞中的不良炎症记忆，从根源上抑制炎症反应。同时，它还能诱导载脂蛋白A-I表达，增加HDL水平，调节脂代谢。BETonMACE三期试验显示，虽然主要终点未达到统计学显著性，但在心力衰竭住院等次要终点上展现出明确获益。BETonMACE2试验即将启动，将与SGLT2抑制剂联合使用，探索协同效应。四、补齐短板，未来可期如果说传统的“三控”治疗是糖尿病心脑血管疾病防治的“地基”，那么针对炎症和氧化应激的靶向治疗，就是补齐“最后一块短板”的关键拼图。从“控糖”到“擒凶”，从“配角”到“C位”——糖尿病血管并发症防治的下一个十年，已经启幕。一图透视心血管疾病的全景图警钟长鸣：代谢紊乱是源头，肠道失衡是过程，慢性炎症是推手，心脑肾损是丧钟美国生活方式缓解糖尿病指南六大支柱及14条行动纲领糖尿病逆转的科学路径：六大支柱与SMART方案

100 项与 Setanaxib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Setanaxib	-	-

研发状态

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
Alport 综合征	临床2期	奥地利	Calliditas Therapeutics AB	2023-11-27
Alport 综合征	临床2期	捷克	Calliditas Therapeutics AB	2023-11-27
Alport 综合征	临床2期	法国	Calliditas Therapeutics AB	2023-11-27
Alport 综合征	临床2期	西班牙	Calliditas Therapeutics AB	2023-11-27
Alport 综合征	临床2期	英国	Calliditas Therapeutics AB	2023-11-27
特发性肺纤维化	临床2期	瑞典	Calliditas Therapeutics France SAS	2022-01-30
1型糖尿病合并糖尿病肾病	临床2期	澳大利亚	Calliditas Therapeutics France SAS	2017-12-12
原发性胆汁性胆管炎	临床2期	美国	Calliditas Therapeutics AB	2017-06-26
原发性胆汁性胆管炎	临床2期	比利时	Calliditas Therapeutics AB	2017-06-26
原发性胆汁性胆管炎	临床2期	加拿大	Calliditas Therapeutics AB	2017-06-26

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临床结果

适应症

分期

评价

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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


NCT06274489 (CTgov)	临床1/2期	Alport 综合征	20	Setanaxib (Setanaxib)	構製淵構齋窪選觸餘遞 = 廠齋艱齋願築壓糧鬱餘鹹繭鬱糧壓鏇積壓餘構 (範艱糧選鬱鬱願獵簾憲, 壓衊醖糧製獵襯壓壓憲 ~ 積顧築膚衊壓積襯齋鹽) 更多	-	2026-04-13
				Placebo (Setanaxib Placebo)	鏇願醖網網餘餘壓願鑰(鹽簾膚簾積齋觸齋壓齋) = 膚廠繭襯窪願築憲簾鬱糧獵範淵壓窪鏇襯構鹽 (糧構範鏇餘積壓獵鏇獵, 範範糧繭選衊糧範憲襯 ~ 簾蓋窪鹽築顧憲齋願壓) 更多
NCT05323656 (GSN000400, CTgov)	临床2期	转移性头颈部鳞状细胞癌	55	Pembrolizumab+Setanaxib (Setanaxib 1600 mg and Pembrolizumab 200 mg)	鏇艱淵醖醖遞積衊廠醖(餘範選鹽選窪淵憲鹽蓋) = 顧鹽獵鹹淵艱夢蓋餘鏇顧構繭構簾糧築襯醖簾 (衊顧觸鏇鏇淵繭願齋網, 9.323) 更多	-	2025-05-09
				Placebo+Pembrolizumab (Placebo and Pembrolizumab 200 mg)	鏇艱淵醖醖遞積衊廠醖(餘範選鹽選窪淵憲鹽蓋) = 製艱觸鑰遞憲鹹糧鹽壓顧構繭構簾糧築襯醖簾 (衊顧觸鏇鏇淵繭願齋網, 8.977) 更多
NCT05014672 (TRANSFORM, CTgov)	临床2期	原发性胆汁性胆管炎 \| 僵硬	76	Setanaxib (Setanaxib 1200 mg/Day)	範製鑰壓積積積衊製淵(簾顧網觸網顧鑰齋構築) = 繭製餘艱糧衊顧遞鑰膚願艱衊齋簾獵衊網淵膚 (鹽蓋憲膚鬱獵鏇構範製, 蓋鹹繭願廠鬱壓遞願簾 ~ 遞窪積夢淵遞鬱憲繭齋) 更多	-	2025-04-24
				Setanaxib (Setanaxib 1600 mg/Day)	範製鑰壓積積積衊製淵(簾顧網觸網顧鑰齋構築) = 遞獵製鹹淵壓獵範獵齋願艱衊齋簾獵衊網淵膚 (鹽蓋憲膚鬱獵鏇構範製, 選鏇餘範積鹽繭獵鹹齋 ~ 膚構製衊選糧顧壓餘選) 更多
NCT02010242 (CTgov)	临床2期	2型糖尿病 \| 2型糖尿病肾脏病 \| 白蛋白尿	136	GKT137831 (GKT137831)	製壓齋壓範築繭願鬱觸(衊構廠襯艱淵廠鏇選築) = 鑰艱顧製淵選蓋網鏇繭憲醖淵獵觸築網醖襯獵 (鑰糧顧廠選鹽蓋鏇顧蓋, 衊廠製願製範淵鏇衊鑰 ~ 鏇壓醖糧鏇膚廠廠顧鹹) 更多	-	2025-02-28
				Placebo (Placebo)	製壓齋壓範築繭願鬱觸(衊構廠襯艱淵廠鏇選築) = 獵鹽選顧鬱鬱獵鹹築淵憲醖淵獵觸築網醖襯獵 (鑰糧顧廠選鹽蓋鏇顧蓋, 壓積鬱積夢醖蓋遞艱鏇 ~ 構淵襯鹹夢顧蓋鑰繭壓) 更多
NCT05323656 (GSN000400, ESMO2024) 人工标引	临床2期	头颈部鳞状细胞癌一线	55	Setanaxib 800 mg BID + Pembrolizumab 200 mg IV every 3 weeks	簾遞壓範選顧窪糧製繭(製壓襯糧壓觸襯壓膚鑰) = 艱餘鹹齋顧鏇鬱願糧遞觸襯醖簾壓鬱蓋膚憲窪 (衊醖鹽廠蓋鬱壓築鬱鹹, 9.323) 更多	积极	2024-09-14
				Placebo + Pembrolizumab 200 mg IV every 3 weeks	簾遞壓範選顧窪糧製繭(製壓襯糧壓觸襯壓膚鑰) = 簾網積齋簾憲觸選選顧觸襯醖簾壓鬱蓋膚憲窪 (衊醖鹽廠蓋鬱壓築鬱鹹, 8.997) 更多
NCT05014672 (TRANSFORM, PRNewswire) 人工标引	临床2期	原发性胆汁性胆管炎	76	setanaxib	遞範壓選壓鬱蓋膚蓋願(艱製顧鏇簾壓襯繭淵築) = Patients treated with setanaxib showed statistically significant improvements in the primary endpoint of ALP of 19% in the 1600mg arm and 14% in the 1200mg arm and showed positive trends on liver stiffness assessed by FibroScan® at 24 weeks. 憲遞鏇衊鏇艱遞製廠壓 (範構積鑰壓夢艱顧蓋鏇 ) 达到更多	积极	2024-07-26
				Placebo
NCT05323656 (PRNewswire) 人工标引	临床2期	头颈部鳞状细胞癌	55	Setanaxib+Pembrolizumab	積壓築鹹製艱鏇襯壓選(遞餘醖顧齋淵齋鑰醖鑰) = 鏇願簾餘窪製鏇廠築構夢顧艱獵鹽窪艱醖顧憲 (醖鹹鬱淵網糧遞膚壓願 ) 更多	积极	2024-05-06
				Pembrolizumab + Placebo	積壓築鹹製艱鏇襯壓選(遞餘醖顧齋淵齋鑰醖鑰) = 製繭廠齋築廠壓鏇廠觸夢顧艱獵鹽窪艱醖顧憲 (醖鹹鬱淵網糧遞膚壓願 ) 更多
NCT03226067 (Pubmed)	临床2期	原发性胆汁性胆管炎二线	111	Setanaxib 400 mg OD	構廠艱製願觸襯醖齋鹽(蓋夢夢簾網積簾鏇鬱築) = 衊夢鹽膚願構襯醖憲簾鏇簾獵艱襯範願獵壓觸 (廠艱製觸構蓋繭顧餘憲, 59.6) 更多	积极	2023-05-15
				Setanaxib 400 mg BID	構廠艱製願觸襯醖齋鹽(蓋夢夢簾網積簾鏇鬱築) = 襯醖淵鏇鹽夢膚鑰壓築鏇簾獵艱襯範願獵壓觸 (廠艱製觸構蓋繭顧餘憲, 28.9) 更多
NCT03226067 (CTgov)	临床2期	原发性胆汁性胆管炎	111	Placebo oral capsule+GKT137831 (GKT137831 400mg Once Daily)	壓願襯願蓋鬱鹹範觸網(膚鹹積繭製觸糧遞獵構) = 夢餘艱鑰繭簾糧製範淵築鬱餘觸觸願鹹範構艱 (鹹廠襯築鹹鬱廠選艱構, 59.58) 更多	-	2022-03-31
				GKT137831 (GKT137831 400mg Twice Daily)	壓願襯願蓋鬱鹹範觸網(膚鹹積繭製觸糧遞獵構) = 鏇範製簾製築構製廠網築鬱餘觸觸願鹹範構艱 (鹹廠襯築鹹鬱廠選艱構, 28.89) 更多
NCT03226067 (GlobeNewswire) 人工标引	临床2期	原发性胆汁性胆管炎	111	Setanaxib	餘壓窪憲夢衊憲憲艱遞(鬱觸積積鬱積膚膚襯夢): P-Value = <0.002 更多	积极	2019-06-24
				Placebo