作者: Halilbasic, Emina ; Ohradanova-Repic, Anna ; Bergthaler, Andreas ; Huber, Samuel ; Bock, Christoph ; Scharnagl, Hubert ; Köcher, Thomas ; Kenner, Lukas ; Boucheron, Nicole ; Karlsen, Tom H ; Kunczer, Victoria ; Al-Rubaye, Osamah ; Cavanagh, Lois L ; Waltenberger, Darina ; Schatzlmaier, Philipp ; Zhu, Ci ; Stojakovic, Tatjana ; Stockinger, Hannes ; Schuster, Michael ; Trauner, Michael ; Ellmeier, Wilfried ; Lercher, Alexander ; Muscate, Fanziska ; Thorbjørnsen, Liv Wenche ; Claudel, Thierry ; Chung, Brian K

Background:

24-Nor-ursodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid for treating immune-mediated cholestatic liver diseases, such as primary sclerosing cholangitis (PSC).

Objective:

Since PSC strongly associates with T helper-type-like 17 (TH17)-mediated intestinal inflammation, we explored NorUDCA’s immunomodulatory potential on TH17 cells.

Design:

NorUDCA’s impact on TH17 differentiation was assessed using a CD4+TNaive adoptive transfer mouse model, and on intraepithelial TH17 pathogenicity and transdifferentiation using an αCD3 stimulation model combined with interleukin-17A-fate-mapping. Mechanistic studies used molecular and multiomics approaches, flow cytometry and metabolic assays with pathogenic (p) TH17. Pathogenicity of pTH17 exposed to NorUDCA in vitro was evaluated following adoptive transfer in intestinal tissues or the central nervous system (CNS). Key findings were validated in an αCD3-stimulated humanised NSG mouse model reconstituted with peripheral blood mononuclear cells from patients with PSC.

Results:

NorUDCA suppressed TH17 effector function and enriched regulatory T cell (Treg) abundance upon CD4+TNaive cell transfer. NorUDCA mitigated intraepithelial TH17 pathogenicity and decreased the generation of proinflammatory ‘TH1-like-TH17’ cells, and enhanced TH17 transdifferentiation into Treg and Tr1 (regulatory type 1) cells in the αCD3-model. In vivo ablation revealed that Treg induction is crucial for NorUDCA’s anti-inflammatory effect on TH17 pathogenicity. Mechanistically, NorUDCA restrained pTH17 effector function and simultaneously promoted functional Treg formation in vitro, by attenuating a glutamine-mTORC1-glycolysis signalling axis. Exposure of pTH17 to NorUDCA dampened their pathogenicity and expansion in the intestine or CNS upon transfer. NorUDCA’s impact on TH17 inflammation was corroborated in the humanised NSG mouse model.

Conclusion:

NorUDCA restricts TH17 inflammation in multiple mouse models, potentiating future clinical applications for treating TH17-mediated intestinal diseases and beyond.

2025-06-01·JOURNAL OF HEPATOLOGY

History and prospects of bile acid therapies

Review

作者: Williamson, Catherine ; Keitel, Verena ; Karpen, Saul ; Trauner, Michael ; Beuers, Ulrich ; Banales, Jesus M

Animal bile has been regarded as a potential remedy of liver diseases for millennia in ancient Eastern cultures. The application of bile acids as major organic bile components for gallstone dissolution and of ursodeoxycholic acid (UDCA) for cholestatic liver diseases began in the 2^nd half of the 20^th century. Currently, UDCA is regarded as effective 1^st line treatment of primary biliary cholangitis, the most frequent chronic cholestatic liver disease, and is also applied in other cholestatic disorders including primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy. For the past two decades, nuclear receptor agonists such as the farnesoid-X receptor agonist and chenodeoxycholic acid derivative obeticholic acid and derivatives of UDCA such as norucholic acid and various UDCA hybrids are under evaluation for treatment of diverse benign and malignant, genetic and acquired hepatobiliary disorders. Development of new drugs interacting with the enterohepatic bile acid circulation has attracted attention for rare genetic pediatric disorders. The present review describes the current status and future prospects of bile acid-based therapies for hepatobiliary diseases of adults, children and during pregnancy on the basis of historical developments over centuries and millennia.

2025-01-01·Advances in Pharmacological and Pharmaceutical Sciences

Safety, Tolerability, and Pharmacokinetics of NorUrsodeoxycholic Acid (Shilpa Medicare Limited, India) in Healthy Adults: Results From a Phase I Open-Label Dose-Escalation Study.

Article

作者: Alluri, Chandrasekhar Varma ; Madala, Pavan Kumar ; Dundigalla, Mamatha Reddy ; Panuganti, Veerendra Kumar ; K S S V V, Sanyasirao ; Mohammad, Javeed

NorUrsodeoxycholic acid (norUDCA) is a side-chain-shortened derivative of ursodeoxycholic acid (UDCA) with specific pharmacological properties, including cholehepatic shunting, making it a promising candidate for a range of cholestatic and metabolic liver diseases. This phase I study evaluates the safety, tolerability, and pharmacokinetics of single ascending doses of norUDCA in healthy adults under fasting conditions. In this open-label, dose-escalation study, healthy adults (aged 18-45 years) were enrolled into 3 successive dose escalation cohorts, receiving norUDCA oral tablets of 500 mg (n = 14), 1000 mg (n = 14), and 1500 mg (n = 14) once daily. The primary endpoints were the incidence rate of dose-limiting toxicities (DLTs), assessment of maximum tolerated dose (MTD) after single dose administration, and an establishment of the recommended phase II dose. Secondary endpoints included pharmacokinetic assessments and evaluation of dose proportionality. Following single-dose administration of 500 mg, 1000 mg, and 1500 mg, no DLTs were observed, and the MTD was determined to be 1500 mg/day. Maximum plasma concentration (C _max) and plasma exposure [area under the curve (AUC)] to norUDCA increased dose proportionally from 500 to 1500 mg/day. Median time to achieve maximum plasma concentration (T _max) for norUDCA at 1500 mg/day cohort (3 h) was comparable to 1000 mg/day cohort (3 h) but lower than 500 mg/day cohort (4 h). The half-life was longer in 1500 mg/day (16 h) cohort compared to 500 mg/day (15 h) and 1000 mg/day cohorts (14 h). The 90% confidence interval of the slope estimates for C _max (22.41, 59.70), AUC_0-t (11.71, 61.14), and AUC_0-inf (10.74, 61.86) did not consistently fall within the predefined acceptable limits (79.69, 120.31) for formal dose proportionality criteria. No serious adverse events or deaths occurred in any cohort. One treatment-emergent adverse event was observed (an increase in the white blood cell count), which was not related to the study drug. A single dose of norUDCA is safe and well-tolerated, with favorable plasma pharmacokinetic profiles in healthy subjects. Based on the safety and pharmacokinetic data, the recommended dosage for further clinical trials is 1500 mg/day. Trial Registration: Clinical Trials Registry-India: CTRI/2022/11/047561.

项与去甲熊去氧胆酸相关的新闻（医药）

2025-08-17

·医药经济报

代谢领域喜讯不断！银诺医药港股上市，礼来13亿美元再布局减重，首款肝病疗法获批

1.银诺医药港股上市，开盘大涨285.44% 8月15日，专注于糖尿病和其他代谢性疾病创新疗法的生物制药公司银诺医药成功在港交所主板上市，发行价格18.68港元/股，开盘价72港元/股，开盘大涨285.44%，市值达329亿港元。银诺医药成立于2014年12月5日，是一家专注于糖尿病和其他代谢性疾病创新疗法的生物制药公司。公司核心产品是针对GLP-1R靶点的依苏帕格鲁肽α，一款公司自主研发的人源长效GLP-1受体激动剂，可用于治疗T2D、超重和其他代谢性疾病，能够有效控制血糖水平，帮助控制体重，并对心血管系统、肝脏、肾脏和中枢神经系统有显著的益处。招股书显示，银诺医药已在国内获批将依苏帕格鲁肽α作为单药治疗及联合二甲双胍治疗2型糖尿病(T2D)。两种疗法均已于2025年1月获得批准，并在2月进入商业化阶段（商品名：怡诺轻），在医院、药店及电商平台等渠道销售。截至2025年5月31日止五个月，在中国销售依苏帕格鲁肽α取得入3814万人民币。银诺医药也将其用于治疗肥胖和超重。公司于今年3月在中国启动了用于治疗肥胖和超重的核心产品IIb/III期临床试验，计划将于2026年第四季度完成该试验。 2.礼来达13亿美元小分子疗法合作，减重领域再布局 Superluminal Medicines今日宣布与礼来公司达成合作，共同推进针对未公开G蛋白偶联受体（GPCR）靶点的小分子药物研发，这些靶点与心脏代谢疾病及肥胖密切相关。双方将结合Superluminal的前沿结构驱动药物发现平台与礼来在小分子开发及商业化方面的深厚经验，加速推动疗法进入临床。根据协议，Superluminal将利用其专有平台开展发现与优化工作，礼来将在Superluminal交付符合预设标准的候选化合物后，获得独家开发与商业化权利。Superluminal有望获得最高达13亿美元的款项，包括首付款、近期付款、研发与商业里程碑付款等。据介绍，Superluminal的平台整合了深度结构生物学、机器学习以及专有的药代动力学与毒理学预测工具，可加速发现可进入候选阶段的小分子药物。其早期重点布局在GPCR领域，这类靶点因功能选择性与结构复杂性长期被视为研发挑战，亟需新一代计算解决方案助力突破。此次合作有望加快新药研发进程，并为心脏代谢疾病及肥胖治疗提供了新疗法。 3.全球首个MAFLD疗法获批上市 8月15日，Shilpa Medicare宣布获得了印度中央药品标准控制组织（CDSCO）对500毫克去甲熊去氧胆酸（NorUDCA）片剂的全球首个监管批准，用以治疗代谢功能障碍相关脂肪性肝病（MAFLD）。根据新闻稿，这是MAFLD领域首个获批的治疗方案。 NorUDCA具有创新的双重作用机制，兼具抗炎功效与增强的胆汁酸调节功能。这一创新疗法有望阻止MAFLD恶化为更严重的肝脏疾病，如代谢功能障碍相关脂肪性肝炎（MASH）、肝硬化和肝衰竭。大量临床试验证明NorUDCA在疗效上显著优于安慰剂，且安全性优异，未报告重大不良事件。编辑：余远泽版式编辑：于成林审校：马飞、张松赛诺菲回应波立达停供！恒瑞、康方、君实等围战PCSK9 2025医保商保初审名单透视：礼来、诺和诺德GLP-1混战，吉利德、科伦ADC交锋，卫材、BMS双线突围专利纠纷和解！GSK分羹3.7亿美元，辉瑞/BioNTech认栽买单？ www.yyjjb.com.cn 洞悉行业趋势长按关注医药经济报《中国处方药》学术公众号聚焦药学学术和循证研究长按关注中国处方药《医药经济报》终端公众号记录药品终端产经大事件长按关注21世纪药店

引进/卖出

2025-08-15

·医药健闻

司美格鲁肽加冕上半年“药王”；礼来将其英国市场减肥药价格最高上调170%；罗氏诊断第二款国产病理诊断平台正式获批 | 日报

全球医疗行业每日重点资讯文 | 苏丁企业动态罗氏诊断中国宣布，国产全自动免疫组化染色平台BenchMark GX正式获批。这是继去年国产BenchMark ULTRA PLUS获批上市后，罗氏诊断在中国本土化战略进程中取得的又一重大成果。此次国产BenchMark GX将在位于苏州的罗氏诊断亚太生产基地和研发中心进行本土化生产。该生产基地和研发中心严格遵循罗氏全球统一的质量管理体系，拥有从研发、生产到物流的完整产业链，并已成功实现多款诊断产品的本土化研发和生产。巴菲特旗下伯克希尔哈撒韦公司(Berkshire Hathaway)上季度增持陷入困境的保险公司联合健康集团(UnitedHealth Group)的股份。鉴于该公司目前的声誉，这笔收购令人意外，但考虑到巴菲特的低价投资历史，这或许并非偶然。伯克希尔在6月底以约16亿美元的价格收购了这家医疗保健公司超过500万股股票。这笔股份在伯克希尔投资组合中位列第18大持股。 VML Health任命Jason Reese为全球首席转型官，加强了在先进技术、数据和人工智能战略方面的工作。该职位使Reese成为该机构业务转型和数字创新工作的负责人，包括扩展企业解决方案能力。VML Health正在投资这些领域，以帮助其制药和医疗保健客户简化运营、嵌入人工智能和其他新兴技术并实现预期结果，同时遵守监管要求。药明生物宣布，其超高效连续灌流生产技术平台WuXiUP成功完成中试规模的端到端全自动化原液连续生产，未来将进一步在主要GMP生产基地推广应用。WuXiUP全自动连续生产线通过全线集成自动化系统，可实现24/7小时不间断高效运转，大幅减少人工操作环节，降低产品质量风险，提升生产效率。由上海国际医学中心与复星医视特共建的全国首个“聚焦超声标准治疗示范中心”正式揭牌，标志着我国脑部磁波刀（MRgFUS）技术进入标准化发展新阶段。该中心将通过全流程管理体系建设，推动这一创新疗法在癫痫、抑郁症等领域的临床验证与应用普及。产业动态 2025年上半年全球药品销售TOP50榜单揭晓。诺和诺德的司美格鲁肽以超166亿美元销售额成为“药王”，礼来的替尔泊肽以121.3%的销售增长率展现潜力。作为一种GLP-1受体激动剂类药物，司美格鲁肽包括Ozempic（降糖注射版）、Rybelsus（降糖口服版）和Wegovy（减重版）三大版本，上半年的销售额分别为96.46亿美元、16.79亿美元和54.58亿美元，同比增长分别为15%、5%和78%。礼来宣布，从9月起，将把其在英国广受欢迎的减肥药Mounjaro价格最高上调170%，以回应美国总体特朗普关于“外国搭便车”导致美国药价过高的抱怨。礼来表示，其减重以及治疗2型糖尿病的Mounjaro在英国大幅提价，是为了解决与其他发达国家相比存在的价格不一致问题。不过，该公司强调，此次调价不涉及英国国家医疗服务体系(NHS)的采购价格，以确保药品持续供应。 Superluminal Medicines宣布与礼来达成合作，共同推进针对未公开G蛋白偶联受体（GPCR）靶点的小分子药物研发，这些靶点与心脏代谢疾病及肥胖密切相关。根据协议，Superluminal将利用其专有平台开展发现与优化工作，礼来将在Superluminal交付符合预设标准的候选化合物后，获得独家开发与商业化权利。Superluminal有望获得最高达13亿美元的款项，包括首付款、近期付款、研发与商业里程碑付款等。首届“AI赋能智能化类器官创新与产业发展论坛”暨亚洲首台CellXpress.ai体外模型智能化系统发布会日前在上海举办。亚洲首台CellXpress.ai体外模型智能化系统具有全天候自动化运行，标准化和一致性输出，高效率扩增等革命性突破。通过机器学习辅助监测、培养、成像和调度，实现真正3D生物学全流程自动化，显著提高多种干细胞、细胞3D培养物或类器官的生长和扩增效率，改善筛选工作流程，为推动类器官技术向自动化、标准化迈进。论坛期间，“生物芯片上海国家工程研究中心与美谷分子仪器联合实验室”“智能化类器官创新与产业联盟”“类器官与器官芯片创新研发中心”正式揭牌。维立志博宣布，奥帕替苏米单抗（抗PD-L1/4-1BB双特异性抗体LBL-024）单臂关键注册临床研究已完成全部受试者入组。这是全球首个单药免疫治疗肺外神经内分泌癌（EP-NEC）的注册临床研究，由北京大学肿瘤医院沈琳教授牵头，全国多家医院共同参与，旨在评估奥帕替苏米单抗在既往接受过二线及以上化疗后进展的晚期EP-NEC患者中的有效性和安全性。中红医疗与瑞桥鼎科集团签署战略合作协议，瑞桥鼎科集团授予中红医疗一次性使用无菌硅胶导尿管（普通），一次性使用无菌硅胶导尿管（超滑）、一次性使用无菌硅胶导尿管包、一次性使用无菌超滑硅胶导尿管产品的独家代理权。心脉医疗Minos（定海塔）腹主动脉覆膜支架及输送系统在利比亚成功完成首例临床植入，标志着这款产品正式在该国进入临床应用，公司在非洲市场的业务拓展取得又一重要突破。 Shilpa Medicare Limited获得了印度中央药品标准控制组织（CDSCO）对500毫克去甲熊去氧胆酸（NorUDCA）片剂的全球首个监管批准，这也是NAFLD领域首个获批疗法。NorUDCA具有创新的双重作用机制，兼具抗炎功效与增强的胆汁酸调节功能。这一创新疗法有望阻止NAFLD恶化为更严重的肝脏疾病，如非酒精性脂肪性肝炎（NASH）、肝硬化和肝衰竭。 CSL铁替代疗法Venofer的仿制药经过多年的等待已抵达美国。Viatris和Amphastar Pharmaceuticals均表示，他们的蔗糖铁注射产品已获得FDA的批准，用于治疗慢性肾病患者的缺铁性贫血。在这两种情况下，两家公司都获得了单剂量小瓶中三种剂量强度（50 mg/2.5mL、100mg/5mL 和 200mg/10mL）的Venofer仿制药的批准。联系美通社 +86-10-5953 9500 info@prnasia.com

并购上市批准

2025-08-14

·PRNewswire

Shilpa Medicare's NorUDCA Makes History as First Approved NAFLD Therapy Worldwide

Shilpa Medicare emerges as the global pioneer to receive approval for NorUDCA, offering new hope to over a billion people affected by Non-Alcoholic Fatty Liver Disease (NAFLD) NAFLD affects 1 in 4 people globally (1.2 billion), with 188 million patients in India—most undiagnosed until irreversible damage occurs. A Breakthrough in Liver Health: NorUDCA delivers a novel dual-action mechanism, combining anti-inflammatory benefits with enhanced bile acid regulation. This innovative therapy promises to halt the progression of NAFLD to severe liver conditions such as NASH, cirrhosis, and liver failure. Clinically Proven and Safe: Robust clinical trials demonstrate NorUDCA's significant superiority over placebo in efficacy, with an excellent safety profile and no major adverse events reported RAICHUR, India, Aug. 14, 2025 /PRNewswire/ -- In a landmark moment for global hepatology and Indian pharmaceutical innovation, Shilpa Medicare Limited (BSE: 530661) (NSE: SHILPAMED) has secured the world's first regulatory approval from India's Central Drugs Standard Control Organization (CDSCO) for Nor Ursodeoxycholic Acid (NorUDCA) Tablets 500 mg, the first-ever approved therapy targeting NAFLD. Mr. Vishnukant Bhutada, Managing Director, Shilpa Medicare, hailed the approval as a "transformational leap": "Receiving approval for NorUDCA marks a transformational leap—not only for Shilpa Medicare but for millions silently suffering from liver disease. We are honored to be the first company globally to bring this innovative therapy to patients, reflecting our unwavering commitment to pioneering healthcare solutions and expanding access to life-changing treatments across India and beyond. We are excited to launch NorUDCA in India immediately and are actively pursuing approvals worldwide to ensure this vital therapy reaches patients everywhere in need." Shilpa Medicare is committed to rapidly commercializing NorUDCA in India and pursuing international regulatory pathways, aiming to bring this life-altering treatment to patients on a global scale About Shilpa Medicare Limited: Shilpa Medicare Limited is a fully integrated pharmaceutical group specializing in innovative Oncology and Non-Oncology APIs, Peptides, Polymers, New Biological Entities and differentiated finished dosage formulations such as Orally Dispersible Films and Transdermal Patches. The company offers end-to-end CDMO services to global pharmaceutical partners, supported by four advanced R&D centers and seven manufacturing facilities, consistently driving innovation and quality in healthcare. Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准

100 项与去甲熊去氧胆酸相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16260

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
代谢功能障碍相关的脂肪肝病	印度	Shilpa Medicare Ltd.	2025-08-14

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
原发性硬化性胆管炎	临床3期	奥地利	Dr. Falk Pharma GmbH	2017-08-24
非酒精性脂肪性肝炎	临床2期	匈牙利	Dr. Falk Pharma GmbH	2019-04-21

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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


NCT01755507 (Pubmed \| J Hepatol)	临床2期	原发性硬化性胆管炎	159	norUDCA 500mg/d	簾艱夢艱築衊觸範憲窪(衊鑰積鹽憲積衊齋衊網) = 顧夢構範製艱構願襯蓋獵鏇鹹蓋艱選顧選醖餘 (淵積簾積淵鬱範襯鏇願 )	-	2017-09-01
				norUDCA 1,000mg/d	簾艱夢艱築衊觸範憲窪(衊鑰積鹽憲積衊齋衊網) = 膚衊網構襯簾膚鑰夢鏇獵鏇鹹蓋艱選顧選醖餘 (淵積簾積淵鬱範襯鏇願 )