A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study to Evaluate the Safety, Tolerability, and Efficacy of Olorinab in Subjects With Irritable Bowel Syndrome Experiencing Abdominal Pain

The purpose of this study is to determine whether olorinab is a safe and effective treatment for abdominal pain in participants with irritable bowel syndrome (IBS).

开始日期2019-07-24

申办/合作机构

Arena Pharmaceuticals, Inc.

NCT03155945

/ Completed临床2期

A Randomized, Open-label, Parallel, Phase 2a Study to Determine the Tolerability, Pharmacokinetics, and Efficacy of APD371 in Participants With Crohn's Disease Experiencing Abdominal Pain

The purpose of this randomized, open-label, parallel, phase 2a study is to determine the tolerability, pharmacokinetics, and efficacy of olorinab in participants with Crohn's disease experiencing abdominal pain.

开始日期2017-07-19

申办/合作机构

Arena Pharmaceuticals, Inc.

100 项与 Olorinab 相关的临床结果

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100 项与 Olorinab 相关的转化医学

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100 项与 Olorinab 相关的专利（医药）

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项与 Olorinab 相关的文献（医药）

2025-12-01·PHARMACOLOGICAL RESEARCH

Kinetic multiplex assay to assess biased signaling of clinical GPCR agonists

Article

作者: van der Horst, Cas ; de Koning, Elisa J M ; Grether, Uwe ; Wittwer, Matthias B ; Bouma, Jara ; Kumar, Sanjay Sunil ; van den Berg, Barry J W ; van der Stelt, Mario ; Guba, Wolfgang ; Rufer, Arne C ; Hoare, Samuel R J ; Heitman, Laura H

Studying biased signaling of G protein-coupled receptors (GPCRs) holds promise for the identification of ligands with a better therapeutic window. However, proper examination of biased signaling remains challenging by risking introduction of system or observation bias. Therefore, we developed a novel multiplex assay that simultaneously and kinetically detects cAMP production and ß-arrestin-2 recruitment in the same well. To investigate the applicability of the kinetic multiplex assay, we profiled seventeen clinically tested agonists for the cannabinoid CB₂ receptor (CB₂R), a promising GPCR for treating tissue injury and inflammation. Agonist-mediated CB₂R activation and signaling was time sensitive, dependent on the agonist. Similar potency and efficacy parameters were obtained from semi-kinetic and kinetic analysis, while the latter provided additional signaling rate constants for signaling onset (k₁) and decline (k₂). Fast CB₂R engagement (k_on) of agonists resulted in increased affinity and potency. Slow dissociation of agonists extended the interaction between CB₂R and ß-arrestin-2. Moreover, superagonists Tedalinab, Olorinab, PRS-211375 and ART-27.13 were characterized by fast k₁ values. No significant biased signaling was observed for the investigated CB₂R agonists. To validate the assay, the reported biased compound JWH145 was tested in a multiplex assay developed for CB₁R and confirmed that our new method is able to detect bias. Altogether, this study accentuates the potential of multiplexing functional responses and performing kinetic analyses to provide an extensive preclinical profile for agonists that may better predict their in vivo pharmacological effects. Ultimately, providing full kinetic context for binding and signaling of GPCR agonists could advance drug discovery efforts.

2025-06-03·Expert opinion on investigational drugs

Targeting diarrhea-predominant irritable bowel syndrome: hopes or hypes?

作者: Bassotti, Gabrio

Since the overall number of patients recruited for these studies was quite low, more robust studies involving a higher numbers of subjects are needed before recommending ondansetron as a treatment of IBS-D.

2024-12-01·EUROPEAN JOURNAL OF PHARMACOLOGY

A combination of peripherally restricted CB1 and CB2 cannabinoid receptor agonists reduces bladder afferent sensitisation in cystitis

Article

作者: Zagorodnyuk, Vladimir ; Yew, Wai Ping ; Ramsay, Stewart ; Brookes, Simon

Cannabinoid agonists can potentially ameliorate lower urinary tract symptoms (LUTS), including pain associated with interstitial cystitis/bladder pain syndrome (IC/BPS). This study aims to determine the contributions of the cannabinoid 1 receptors (CB₁Rs) and CB₂Rs in regulating the activity of different functional classes of afferents, comparing normal healthy bladder with bladders from guinea pigs with protamine/zymosan-induced cystitis. The mechanosensitivity of different functional afferent classes was determined by ex vivo single-unit extracellular recordings. Peripherally restricted CB₁R preferential agonists, ACEA and PrNMI and peripherally restricted CB₂R selective agonists, 4Q3C and olorinab all reduced the mechanosensitivity of mucosal bladder afferents. The potency and efficacy of these synthetic cannabinoid agonists were significantly increased in cystitis compared to controls. Combined application of CB₁R agonists, ACEA or PrNMI with the CB₂R agonist, 4Q3C produced additive inhibitory effects. ACEA and PrNMI also inhibited the stretch-induced firing of high-threshold muscular bladder afferents in animals with cystitis. In contrast, low- and high-threshold muscular-mucosal bladder afferents were unaffected by the CB₁R and CB₂R agonists in control and cystitis. Our data indicated that peripherally restricted CB₁R and CB₂R agonists effectively reduce the sensitisation of probable nociceptive afferents in the bladder in cystitis. The findings also suggest a potential benefit of simultaneously targeting both the CB₁Rs and CB₂Rs to ameliorate LUTS in cystitis.

项与 Olorinab 相关的新闻（医药）

2026-06-16

·EINPresswire

GreenSpace Labs Reports Positive Phase 2 Pilot Data for CBD-Based IBS Therapy GSL-01-001

Clinical-stage company targets 2028–2029 IBS patent cliff with mechanism-distinct cannabinoid approach MIDDLETOWN, RI, UNITED STATES, June 16, 2026 / EINPresswire.com / -- GreenSpace Labs, Inc. (GSL), a clinical-stage pharmaceutical company developing cannabinoid therapeutics for gastrointestinal disorders, today announced preliminary results from its Phase 2 pilot trial evaluating GSL-01-001, an oral cannabidiol-based formulation for irritable bowel syndrome (IBS). The 12-week, single-site study enrolled 23 adult IBS patients, with 13 completing the full treatment period. Data were collected via electronic capture, patient diaries, and site-administered questionnaires. Key Findings Symptom improvement across all domains. Average weekly scores for pain, discomfort, bloating, cramping, and nausea showed consistent declines from baseline through week 12. Pain and discomfort scores dropped from approximately 4.0–4.5 at baseline to 1.5–2.0 by the final study weeks on a 5-point scale. Maintained stool consistency. Average Bristol Stool Form Scale scores remained in the normal range (approximately 4.0) throughout the study, indicating no deterioration in bowel function. Quality of life gains. The proportion of participants reporting IBS symptoms impacted them "Extremely" or "Quite a Bit" fell from 51% at baseline to 10% by week 8. Participants reporting minimal or no impact increased from 32% at baseline to 73% at week 8. Overall health improvement. No participants rated their health as "Excellent" or "Very Good" at baseline. By week 12, six participants reported "Very Good" or "Excellent" overall health. Strategic Positioning GSL is advancing its IBS program ahead of what the company believes is the largest concurrent loss-of-exclusivity event in the modern history of branded IBS therapeutics. Three leading branded products—Xifaxan (Bausch Health), Viberzi (AbbVie), and Linzess (AbbVie/Ironwood)—face generic launches within a 13-month window beginning mid-2028. The global IBS treatment market exceeds $3.6 billion and is growing at approximately 9% annually. GSL-01-001 is designed to address a persistent clinical gap: durable, multi-pathway control of visceral abdominal pain. Current approved IBS therapies do not directly target pain pathways—pain relief is a downstream effect of bowel-habit normalization. GSL's cannabinoid approach engages multiple components of the gut-brain axis. The formulation is further informed by the failure of olorinab, a single-mechanism CB2 agonist that did not demonstrate efficacy in Pfizer/Arena's Phase 2b CAPTIVATE trial, underscoring the need for multi-target cannabinoid pharmacology. Management Commentary "The directional trend we observed across every symptom domain is consistent with our mechanistic hypothesis for GSL-01-001," said William Albro, Chief Executive Officer. "We anticipated this pilot would be hypothesis-generating rather than registration-enabling, and that is exactly what the data show. We now have clear protocol improvements to implement and a defined timeline to execute a GCP-compliant Phase 2 program aligned with the 2028–2029 IBS patent cliff." Partnership Opportunity GSL is seeking a mid- to large-cap pharma partner with existing cannabinoid or GI franchise capabilities for pivotal-stage execution and commercial launch. The company is considering exclusive worldwide licensing, co-development, or full acquisition structures. About GreenSpace Labs, Inc. GreenSpace Labs is a clinical-stage pharmaceutical company developing differentiated cannabinoid therapeutics for functional gastrointestinal disorders . The company's lead asset, GSL-01-001, is an oral CBD-based formulation targeting IBS with potential expansion into IBD-associated pain, functional dyspepsia, and post-infectious GI pain syndromes. Richard Bailey GreenSpace Labs rbailey@greenspacelabs.com Visit us on social media: LinkedIn Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

2025-12-16

·pharmacological research前沿

精选 | Research articles highligted in Dec.

点击上方“蓝字”关注本公众号 Pharmacological Research前沿第178期导语《Pharmacological Research》的最新精选文章出炉啦，本次推送为大家带来了 14篇文章，让我们一起来看看吧！ 01 探究负载DACHPt的生物材料纳米颗粒用于结直肠癌腹膜转移的免疫调节性腹腔化疗 Giuseppina Catania, Serena Zilio, Naoual Bakrin, Giulia Guerriero, Jacqueline Sidi-Boumediene, Emmanuel Chautard, Myriam Kossai, Katrien Remaut, Ragna Haegebaert, David Kryza, Giovanna Lollo 加压腹腔雾化化疗作为治疗结直肠癌腹膜转移的创新疗法，能够将高浓度药物扩散至整个腹腔并降低全身副作用。然而，其疗效受到腹腔内药物快速清除及对肿瘤结节靶向性不足的影响。本研究采用负载二胺环己烷铂的透明质酸-聚精氨酸纳米颗粒进行局部加压治疗，通过对比游离奥沙利铂及其活性组分DACHPt经纳米颗粒递送后的抗肿瘤与免疫调节活性，发现经微流控技术制备的DACHPt NPs在体外对小鼠结直肠癌细胞的细胞毒性显著优于奥沙利铂溶液。在PIPAC治疗的CT26腹膜转移小鼠模型中，DACHPt NPs展现出更优越的抗癌效果，其作用机制与免疫调节特性相关：相较生理盐水组，DACHPt NPs能显著降低脾脏、腹腔液及肿瘤结节中的粒细胞比例，同时提升肿瘤结节内CD8+T淋巴细胞比例至5.5%。研究结果表明，DACHPt NPs不仅抗癌效果优于奥沙利铂溶液，还能重塑免疫抑制微环境，增强抗肿瘤免疫应答。长按识别右侧二维码以查看全文 02 巴利森苷A通过调节肠道菌群增强肠道EAAT3活性以降低血氨水平改善肝性脑病 Jin-Yue Lu, Heng-Tong Zuo, Ru Feng, Yi-Lin Chen, Meng-Liang Ye, Hui Xu, Jia-Chun Hu, Jian-Ye Song, Yi Zhao, Jing-Yue Wang, Jing-Yu Jin, Tie-Feng Yuan, Wan-Xia Wang, Yi-Fan Zhao, Yong-Mei Tu, Ling-Yu Wei, Ming-Yang Li, Bin Cong b c, Jian-Dong Jiang, Yan Wang 肝性脑病是一种与肝功能失调相关的神经精神疾病，其发病机制与肠道菌群密切相关，但治疗手段仍有限。从天然植物天麻中分离的酚类化合物巴利森苷A具有神经保护潜力，目前已进入II期临床试验。本研究首次揭示巴利森苷A通过肠道菌群介导的机制改善肝性脑病的作用路径：巴利森苷A可被肠道菌群特异性代谢为活性产物M2和M3，并通过富集丁酸梭菌和长双歧杆菌，促进肠道谷氨酸生成，同时上调肠道EAAT3的表达，加速谷氨酸进入门脉循环，从而增强肝脏对谷氨酸的摄取。巴利森苷A还能提升肝脏谷氨酰胺合成酶活性，将谷氨酸转化为谷氨酰胺以催化游离氨代谢，进而降低血氨水平。此外，巴利森苷A及其代谢产物通过促进有益短链脂肪酸生成以改善肠道屏障功能，间接减少血氨。上述多重作用共同限制了氨通过血脑屏障进入大脑，最终缓解肝性脑病症状。研究进一步通过口服丁酸梭菌、长双歧杆菌及其组合验证了巴利森苷A的作用机制。该研究首次系统阐释了天然药物通过多种细菌介导的复杂药理机制，为类似天然产物的研究提供了新视角。长按识别左侧二维码以查看全文 03 GLP-1R激动剂的精神活性作用 Loredana Bucciarelli, Vincenzo Cimino, Bernardo Dell’Osso, Paolo Fiorina 胰高血糖素样肽-1受体激动剂作为治疗2型糖尿病与肥胖症的成熟药物，在调控血糖、减轻体重及改善心肾功能之外，近期研究显示其通过中枢GLP-1受体可能产生神经精神与神经保护作用。本综述整合临床前研究、临床试验及真实世界证据，系统阐述了GLP-1R激动剂在抑郁症、焦虑症、暴食症、认知障碍、痴呆以及涉及酒精、尼古丁、可卡因与阿片类物质的成瘾行为中的应用潜力。相关机制涉及神经炎症调节、神经递质系统干预及奖赏通路调控。现有初步结论虽具前景，但受限于小样本、方法学异质性及短期随访等缺陷。未来需通过设计严谨、采用标准化精神类评价终点的随机试验进一步验证。若获证实，GLP-1RAs有望成为跨越代谢疾病与精神健康领域的创新治疗选择。长按识别右侧二维码以查看全文 04 何首乌植物源性外泌体样纳米颗粒通过miRNA递送调控雄激素通路的跨物种传递机制促进毛发生长 Shaojin Li, Youbo Zhang, Xiyang Liu, Huang Su, Haiyan Cao, Hong Xuan, Yingxian Cui, Zengyi Lu, Qinhao Zhang, Yike Li, Xiaoyan Liu, Xiaoai Bao, Hailong Xu, Yanlin Wang, Xinjie Zhuo, Xinyue Zhang, Qingying Zhang, Liqin Zhang 植物源性外泌体样纳米颗粒作为具有跨物种递送和基因调控潜力的新型纳米载体，其生理功能尚待深入探索。本研究从何首乌中分离并表征了外泌体样纳米颗粒，揭示了其通过跨物种递送及对雄激素信号的基因调控作用促进毛发生长的机制。PMENs可经小窝蛋白和硫酸乙酰肝素蛋白聚糖介导的内存作用高效进入真皮乳头细胞，并递送植物源miRNA直接靶向人体雄激素受体，从而下调受体表达并抑制Wnt/β-catenin通路关键抑制因子DKK1。同时，PMENs通过增强GSK3β磷酸化以稳定β-catenin，促进毛囊再生。在睾酮诱导的C57BL/6小鼠毛发再生延迟模型中，PMENs表现出优于米诺地尔的促毛发生长效果。高通量测序鉴定出aof-miR168a与osa-miR164a为核心效应miRNA，两者通过保守的3′UTR结合位点抑制雄激素受体表达。本研究证实PMENs可作为新型miRNA介导的纳米疗法，实现跨物种基因调控，为雄激素性脱发等雄激素相关疾病提供了创新治疗策略。长按识别左侧二维码以查看全文 05 多组学研究射血分数保留型心力衰竭中的糖代谢性心功能障碍 Susanna Longo, Rocco Mollace, Viviana Casagrande, Loredana Bucciarelli, Eugenio Martelli, Rossella Menghini, Jose Manuel Fernández-Real, Massimo Federici 射血分数保留型心力衰竭是一种由心肌组织复杂生化改变引发的综合征，其中代谢灵活性丧失作为不健康心肌的典型特征可能在其进展中起关键作用，但具体代谢改变对HFpEF发展的影响及其与临床表现异质性的关系尚不明确。HFpEF的高度异质性为研究与诊疗带来挑战，亟需深入解析其病理机制并精确区分表型。以人工智能和机器学习为驱动的多组学技术为此提供了新思路，能揭示以往难以探知的HFpEF代谢变化与表型特征，并通过挖掘超越基础临床与人口学指标的非传统生物标志物，推动针对特定患者群体的靶向治疗研发。本综述旨在探讨当前对心肌代谢改变及代谢僵化在HFpEF发病机制中作用的认识，结合最新多组学研究，试图构建HFpEF的组学特征谱，以期为疾病诊断、表型分型、风险分层及个体化疗法开发提供新型生物标志物，从而推动HFpEF领域的精准医疗发展。长按识别右侧二维码以查看全文 06 探究KRAS信号再激活稳定CDC7损害KRAS突变型结直肠癌的化疗敏感性KRAS Ruilin Wu, Yue Liu, Junwei Fu, Tianhua Zhou, Ronggui Hu, Bo Yang, Qiaojun He, Tao Yuan, Hong Zhu 作为结直肠癌中最常见的突变致癌基因，其治疗面临严峻挑战。尽管5-氟尿嘧啶和奥沙利铂仍是KRAS突变型结直肠癌化疗的基础方案，但内在及获得性耐药常限制其疗效。揭示两者敏感性的共同机制可为恢复化疗敏感性提供新策略。本研究发现，细胞分裂周期蛋白7是KRAS突变型结直肠癌化疗反应的关键调控因子。机制上，基因毒性应激触发KRAS-MAPK/PI3K通路的适应性再激活，两者通过破坏HRD1介导的细胞质降解并促进CDC7核转位来协同稳定CDC7蛋白。增加的核内CDC7库容许可DNA损伤耐受，该应激适应过程是5-FU与奥沙利铂产生耐药的共同机制。遗传敲除或药物抑制CDC7能减弱结直肠癌细胞增殖，并在体外和体内实验中显示出与化疗的协同效应。重要的是，本研究阐明了基因毒性应激下CDC7的亚细胞分布及蛋白质稳态调控机制，这是决定KRAS突变型结直肠癌化疗敏感性的关键开关。这些发现确立了CDC7作为KRAS突变型结直肠癌的治疗薄弱点，并为靶向CDC7以恢复5-FU/奥沙利铂化疗敏感性提供了理论依据。长按识别左侧二维码以查看全文 07 评估临床GPCR激动剂偏向信号传导的动力多重分析 Jara Bouma, Elisa J.M. de Koning, Cas van der Horst, Sanjay Sunil Kumar, Barry J.W. van den Berg, Samuel R.J. Hoare, Matthias B. Wittwer, Wolfgang Guba, Arne C. Rufer, Uwe Grether, Mario van der Stelt, Laura H. Heitman 研究G蛋白偶联受体的偏向信号传导有助于发现治疗窗口更优的配体，但现有方法易引入系统或观测偏差。为此，我们开发了一种新型多重动力学分析技术，可在同一微孔中同步实时检测cAMP生成与β-arrestin-2募集。通过对大麻素CB2受体的17种临床阶段激动剂进行表征，发现其介导的激活与信号传导具有时间敏感性及激动剂依赖性。半动力学与全动力学分析得出的效价和效能参数基本一致，而后者额外提供了信号起始速率常数k1与衰减常数k2。激动剂与CB2R的快速结合可提升亲和力与效价，慢解离则延长受体与β-arrestin-2的相互作用。超级激动剂Tedalinab、Olorinab、PRS-211375和ART-27.13均表现出快速的k1值特征，但所有测试激动剂均未显示显著偏向信号。为验证方法通用性，我们在针对CB1R开发的多重分析中测试了已报道的偏向性化合物JWH145，证实该方法具备检测偏向信号的能力。本研究凸显了多重功能响应与动力学分析联用的潜力，可为激动剂提供更全面的临床前特征谱，从而更精准预测其体内药理效应。最终，为GPCR激动剂的结合与信号传导提供完整动力学背景，有望推动药物研发进程。长按识别右侧二维码以查看全文 08 从饮食、肠-脑轴与代谢-表观基因组-免疫网络的交互作用三重维度进行神经疾病管理 Yishu Fan, Bo Xiao, Honghao Zhou, Zhaoqian Liu, Leli Wang, Weilin Jin, Yulong Yin, Xiaoyuan Mao 神经系统疾病是全球致残的主要原因，对个人和医疗系统造成沉重负担。在各种治疗策略中，饮食干预作为一种非药物疗法备受关注。特定膳食模式和营养素通过增强认知功能、延缓疾病进展，在促进大脑健康中发挥关键作用。最新研究指出，调节代谢-表观基因组-免疫网络及肠-脑轴是饮食影响神经系统的两大核心机制。研究提出，饮食干预可通过重塑代谢-表观基因组-免疫网络改善脑功能；另有多项研究表明，营养素能通过肠-脑轴调控神经疾病进程，改善临床结局。本综述从"脑优先"与"体优先"双视角，汇总了当前支持饮食干预神经疾病管理的证据，重点阐释了饮食影响神经系统的双重机制通路。长按识别左侧二维码以查看全文 09 中医通过调节肠道菌群在癌症免疫治疗中的作用机制及应用现状 Heyun Tao, Kexin Mao, Zishu Zhang, Wenjie Wei, Xinyi Huang, Yating Chen, Si Mei, Xuefei Tian 癌症免疫治疗因耐药性问题面临显著局限。目前研究证实，肠道菌群通过调控肿瘤免疫微环境成为抗肿瘤免疫的关键调节因子。传统中医遵循"扶正祛邪"原则，通过多靶点系统调控发挥治疗作用，其中中医药通过调节肠道微生态，进而影响微生物代谢产物的生成，最终实现肿瘤免疫微环境的重编程。本综述系统阐述了不同免疫表型中"中医-肠道菌群-代谢物-免疫细胞-肿瘤免疫微环境"的因果链式关系，重点解析了中药活性成分及经典方剂如何通过重塑微生物群落、富集有益菌群、调控代谢通路来增强癌症免疫治疗效果。尽管临床前数据颇具前景，但受机制复杂性、标准化缺失及临床转化不足等因素制约，该领域仍面临挑战。长按识别右侧二维码以查看全文 10 内质网应激感受器PERK通过破坏线粒体相关内质网膜介导的线粒体稳态并促进线粒体活性氧积累驱动急性心肌梗死中的铁死亡 Xueshu Tao, Yunxiang Zhang, Jiao Pang, Zihan Liao, Gaohan Chen, Xue Zhong, Xingrui Cao, Ying Lin, Dawei Guan, Yuan Tian, Liang Hao, Rui Zhao, Zhipeng Cao 急性心肌梗死作为一种危及生命的疾病，其中心肌细胞的铁死亡是一种重要调控性死亡形式，但其上游调控机制尚未完全明确。本研究探索了内质网应激感受器PERK在缺血损伤中调控铁死亡的作用。通过心脏特异性PERK敲除小鼠、氧糖剥夺处理的心肌细胞及AMI患者心肌组织样本，我们检测了心脏损伤反应、线粒体功能、铁死亡相关蛋白表达以及PERK与线粒体融合蛋白MFN2的相互作用。研究发现，在人类和小鼠的AMI心脏中PERK表达与激活均显著增强。PERK的激活会破坏线粒体-内质网膜接触结构，引发线粒体去极化和过度氧化应激，同时抑制关键抗氧化蛋白，从而促进铁死亡。相反，PERK基因敲除或药物抑制可保护线粒体完整性、恢复氧化还原稳态、缩小梗死面积并改善心功能。机制上，PERK通过与MFN2相互作用调控MAMs稳定性，转录组分析及人类样本验证支持PERK-MAMs-线粒体活性氧轴在缺血损伤中的核心作用。这些发现表明PERK通过破坏MAMs稳定性并增强线粒体氧化应激驱动心肌细胞铁死亡，提示PERK是AMI治疗的潜在靶点。长按识别左侧二维码以查看全文 11 传统与新一代大麻素配体的研发及治疗潜力 Verónica Muñoz-Canales, Bellinda Benhamú, Mar Martín-Fontecha, Henar Vázquez-Villa, Silvia Ortega-Gutiérrez 内源性大麻素系统是一个在多种生理过程中起关键作用的复杂网络，通过大麻素配体对其进行调控已成为药理学研究热点。大麻素受体作为G蛋白偶联受体，可与多种配体相互作用，包括正构激动剂/拮抗剂以及变构调节剂和偏向性调节剂。本综述系统阐述了大麻素受体配体的研发进展：从植物大麻素和内源性大麻素等天然配体出发，这些化合物为早期合成经典大麻素的设计提供了基础，进而发展出结构独特的非经典大麻素；在此基础上，进一步探讨了变构与偏向性调节剂这一拓展领域。长按识别右侧二维码以查看全文 12 Mdivi-1促进脂滴与线粒体的接触，并减轻高脂饮食小鼠的心脏脂毒性 Zujie Xu, Zheying Ma, Huiqian Ren, Yaming Yang, Xiaoqin Zhao, Bing Zhang 本研究旨在探究线粒体分裂抑制剂Mdivi-1能否通过恢复高脂饮食喂养小鼠的脂滴-线粒体接触来缓解心脏脂毒性。在体内实验中，高脂饮食喂养的雄性C57BL/6小鼠经腹腔注射Mdivi-1八周；体外实验中，H9C2心肌母细胞先暴露于棕榈酸诱导环境，再接受Mdivi-1处理。研究综合评估了心脏功能，并进行分子、生化、组织学、细胞及形态学分析。结果显示，Mdivi-1治疗对高脂饮食小鼠的代谢紊乱和心功能障碍具有保护作用。其通过上调Plin2和Plin5表达促进脂滴-线粒体接触，从而缓解心脏脂毒性。进一步研究发现，棕榈酸能以剂量依赖性方式破坏H9C2细胞的脂滴-线粒体接触并诱导脂毒性，而Mdivi-1能有效抑制棕榈酸诱导的线粒体分裂，恢复脂滴-线粒体接触，并促进脂肪酸从脂滴转运至线粒体进行氧化代谢。综上所述，本研究发现Mdivi-1是一种新型心脏保护剂，能够改善心脏脂毒性并促进脂滴-线粒体接触。长按识别左侧二维码以查看全文 13 乳香黄连木疗法治疗功能性消化不良的随机三向交叉临床试验 Stamatia-Angeliki Kleftaki, Charalampia Amerikanou, Chara Tzavara, Theodora Biagki, Demetra Sigala, Alexandra Bouziou, Stamatiki Zouboulaki, Aikaterini Koutsia, Elvira-Victoria Smyrnioudis, Panagiotis Anapliotis, Andriana C. Kaliora 功能性消化不良是一种以慢性上腹部症状和复杂病理生理为特征的常见胃肠道疾病。乳香黄连木是一种具有抗氧化、抗炎及益生元特性的天然树脂，其中乳香黄连木水提物包含水溶性成分与微量精油。本研究通过在希腊雅典开展的一项随机三向交叉试验，旨在评估乳香黄连木及其水提物对缓解功能性消化不良症状与改善生活质量的疗效。依据罗马IV标准并经鉴别诊断确诊的成年志愿者在签署书面同意书后入组，经历为期各四周、间隔两周洗脱期的三个阶段干预：（A）乳香黄连木胶囊；（B）乳香黄连木水提物；（C）无干预阶段。主要结局通过鲁汶餐后不适量表进行评估，次要结局包括生活质量、焦虑水平及用药变化。统计分析采用意向性治疗原则。结果显示，与无干预阶段相比，乳香黄连木及其水提物均显著改善功能性消化不良的症状。其中乳香黄连木有效减轻上腹胀满、上腹烧灼感与胃灼热，而水提物则显著提升生活质量。长按识别右侧二维码以查看全文 14 探究癌症中脂滴与自噬的交互作用 Xiaofen Li, Jiwen Zhang, Shiping Luo, Xiaoqin Yu, Chuangui Song 代谢重编程是癌细胞适应严苛肿瘤微环境的核心策略，涉及对能量代谢、脂质代谢和应激反应的精细调控。其中，脂滴介导的脂质储存与自噬驱动的细胞回收过程之间存在深刻的双向交互作用。脂滴作为动态细胞器，已超越单纯脂质储存功能，成为关键的代谢与信号枢纽；自噬作为基本降解系统，通过自噬体包裹细胞物质在应激时提供必需代谢物。这两条通路深度交织：脂滴不仅为自噬体形成提供脂质和蛋白质，还通过"脂噬"过程被自噬选择性降解，释放的游离脂肪酸驱动线粒体β-氧化，使癌细胞得以耐受缺氧和营养匮乏环境。同时，脂噬通过清除多余脂质防止脂毒性，维持细胞稳态。本研究概述了癌症中脂滴-自噬轴的分子调控机制，探讨其在肿瘤进展、转移和治疗抵抗中的关键作用，并展望靶向该交互节点在未来癌症治疗中的前景。解析这一复杂网络不仅为理解癌症代谢提供了新范式，更为开发靶向肿瘤代谢可塑性与治疗抵抗的新型药物提供了理论依据。长按识别左侧二维码以查看全文编辑 | Zhang 审核 | Chen

临床1期微生物疗法

2021-03-03

·BioSpace

Arena Reconsiders Strategy as CB2 Agonist Misses Primary Endpoint in Phase II

Gastrointestinal and autoimmune company Arena Pharmaceuticals announced mixed topline results for the Phase IIb trial of its oral cannabinoid receptor type 2 (CB2) agonist olorinab. Gastrointestinal and autoimmune company Arena Pharmaceuticals announced mixed topline results for the Phase IIb trial of its oral cannabinoid receptor type 2 (CB2) agonist olorinab, including a miss on its primary endpoint of reducing overall abdominal pain in irritable bowel syndrome (IBS) patients. After the announcement, the company’s stock fell almost 9% to $69.74 this morning. Abdominal pain was measured using the Average Abdominal Pain Score (AAPS), and Arena was looking for improvements in IBS patients with predominant constipation or diarrhea, with a baseline score of 6.5 or higher indicating moderate to severe pain–seen in about half of the study’s 273 participants. Orlinab was given at three doses in the study, three times per day each. At the highest, 50 mg dose, the drug candidate did meet statistical significance, reducing AAPS by 1.64 points compared to placebo, and 3.93 points overall from baseline, at week 12. Consistent with an earlier Phase I trial, olorinab was safe and well tolerated. Almost 80% of IBS patients suffer from recurring or continuous abdominal pain. This was the first Phase II study of a CB2 agonist in IBS pain, says Paul Streck, Senior Vice President for Clinical Development and Chief Medical Officer at Utah-based Arena. “As a Phase 2 trial we were evaluating safety in this population as well as looking for an initial signal of efficacy. We are encouraged by the signal.” The company has not announced orlinab, will be studied in other diseases, but CB2 is known to regulate inflammation, and is being targeted by other companies. Corbus Pharmaceuticals has its oral CB2 agonist lenabasum in a Phase III study for dermatomyositis, and Phase II studies in systemic lupus erythematosus. Last year, Corbus Pharmaceuticals announced lenabasum failed to meet its primary endpoint in a separate Phase III trial for diffuse cutaneous systemic sclerosis, a rare autoimmune disease. In other trials, it showed evidence of reducing inflammation and fibrosis. In addition, Centrexion Therapeutics is currently testing its CB2 agonist, CNTX-6016, in a in Phase Ib/IIa study for diabetic neuropathy. Arena’s lead program is etrasimod, a modulator of another immune target, sphingosine 1-phosphate (S1P) receptor. Etrasimod is in two Phase III trials for ulcerative colitis, and last month Arena launched a Phase II trial in patients with eosinophilic esophagitis, a rare autoimmune-driven digestive disease. On the back of Phase 2b data, the company is also planning a Phase III trial for etrasimod in atopic dermatitis.

临床2期临床结果临床3期

100 项与 Olorinab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11429	Olorinab	-	DB14998

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
便秘型肠易激综合征	临床2期	美国	Arena Pharmaceuticals, Inc.	2019-07-24
腹泻型肠易激综合征	临床2期	美国	Arena Pharmaceuticals, Inc.	2019-07-24
腹痛	临床2期	美国	Arena Pharmaceuticals, Inc.	2017-07-19
克罗恩病	临床2期	美国	Arena Pharmaceuticals, Inc.	2017-07-19

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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


NCT04043455 (CAPTIVATE, CTgov)	临床2期	腹痛 \| 腹泻型肠易激综合征 \| 便秘型肠易激综合征	273	Olorinab (Main Study Period: Olorinab 10 mg)	蓋鬱廠餘構窪積鏇網糧(製廠範顧艱觸獵鹽淵廠) = 築襯鏇鹹蓋遞齋廠餘網壓憲餘構積蓋糧夢觸顧 (構範襯艱選膚廠鹽齋蓋, 0.293) 更多	-	2022-10-12
				Olorinab (Main Study Period: Olorinab 25 mg)	蓋鬱廠餘構窪積鏇網糧(製廠範顧艱觸獵鹽淵廠) = 餘築廠簾衊淵鬱蓋壓蓋壓憲餘構積蓋糧夢觸顧 (構範襯艱選膚廠鹽齋蓋, 0.297) 更多
NCT03155945 (CTgov)	临床2期	腹痛 \| 克罗恩病	14	Olorinab (Olorinab 25 mg TID)	網簾簾艱鏇簾遞簾製憲 = 製顧構餘簾膚鹽鑰膚蓋鹹願糧醖簾餘窪廠鬱遞 (淵醖鏇構顧窪鹽襯廠遞, 糧艱獵鹹齋構築網艱選 ~ 鹹蓋鑰選鑰廠積夢簾齋) 更多	-	2021-11-02
				Olorinab (Olorinab 100 mg TID)	網簾簾艱鏇簾遞簾製憲 = 壓夢餘遞齋顧淵艱選壓鹹願糧醖簾餘窪廠鬱遞 (淵醖鏇構顧窪鹽襯廠遞, 鏇壓製餘選築範網製齋 ~ 衊鹹遞繭蓋鏇夢蓋淵膚) 更多
NCT04043455 (CAPTIVATE, BusinessWire) 人工标引	临床2期	腹痛	273	Olorinab	餘鏇願積壓繭餘遞簾觸(選選窪鹽廠蓋鬱構築鏇) = Moderate to severe pain population at 50 mg showed statistically significant, clinically meaningful improvement vs placebo in Average Abdominal Pain Score (AAPS) 鏇網夢齋獵衊糧齋觸艱 (鏇餘鑰淵膚構壓鏇觸鏇 ) 更多	积极	2021-03-02
				Placebo
ECCO2019	临床2期	-	14	Olorinab 25 mg TID	蓋壓鑰膚鹹鬱夢衊餘遞(簾顧築築夢範糧網廠積) = 繭壓蓋製憲餘廠壓蓋範獵鹹顧製鹽艱繭淵鑰壓 (遞簾夢選襯遞淵鹹憲繭 ) 更多	积极	2019-03-06
				Olorinab 100 mg TID	選製積夢衊築鹹餘壓壓(膚製範簾繭廠製夢鏇糧) = 齋網鹹繭網壓願積夢構齋夢範獵艱範夢醖築醖 (壓齋鹽願鑰製鹹醖積齋 )