The goal of this study is to preliminarily determine/estimate feasibility and whether frequent and early conivaptan use, at a dose currently determined to be safe (i.e., 40mg/day), is safe and well-tolerated in patients with cerebral edema from intracerebral hemorrhage (ICH) and pressure (ICP). A further goal is to preliminarily estimate whether conivaptan at this same dose can reduce cerebral edema (CE) in these same patients. This study is also an essential first step in understanding the role of conivaptan in CE management.
Hypothesis: The frequent and early use of conivaptan at 40mg/day will be safe and well-tolerated, and also reduce cerebral edema, in patients with intracerebral hemorrhage and pressure.

开始日期2017-03-22

申办/合作机构

Allina Health System, Inc.

NCT01954290

/ Withdrawn临床2期IIT

Treatment of Brain Edema and Herniation Secondary to Ischemic or Hemorrhagic Stroke

Stroke remains the fourth leading cause of death in the United States (second worldwide) and a leading cause of long-term disability, resulting in total direct and indirect costs of approximately $73.7 billion annually. The failure of novel therapies in clinical trials demonstrates that the complex neural response to stroke must be targeted at multiple levels to improve patient outcomes. Despite significant improvements in stroke treatment and management, 1 year survival rate among stroke patients aged 65 years or more is around 25%, and 5- year survival rate amounts to approximately 50%. The highest chances of death are within 30 days of stroke. Mortality increases due to worsening brain dysfunction, elevated intracranial pressure (ICP), and other comorbid conditions.
Treatments aimed at reducing post-stroke cytotoxic edema may reduce the risk for development of malignant stroke and mortality. Current treatments such as osmo-therapy and hemicraniectomy have substantial limitations, and mortality remains high, despite these measures outcomes remain unsatisfactory. There is a great need for alternative medical approaches which are safe, predictable, and help to ameliorate post stroke edema.

开始日期2015-09-01

申办/合作机构

University of Florida

NCT01752543

/ Completed临床4期IIT

Effects on Exercise Hemodynamics of Vasopressin Blockade by Conivaptan Infusion in Heart Failure Patients

The purpose of the present study is to evaluate the effects of a blockade of the vasopressin system and central hemodynamic system in heart failure (HF) patients during physical exercise. The significance of the vasopressin system during physical exercise is unclear. If vasopressin is a significant regulator of exercise hemodynamics in HF, strategies to intervene against activation of the V1A-receptor might be expected to improve HF symptoms and possibly outcome.
The potential effects of the central hemodynamic system will be evaluated with a Swan-Ganz catheter. Echocardiography will be performed at rest and during submaximal working capacity before and during the infusion of a vasopressin receptor antagonist (conivaptan) or placebo. Cardiac output will be measured by thermodilution. The exercise test will be performed at 50 % of VO2 max and hemodynamic and echocardiographic measurements will be collected. The exercise test will be performed on a supine multistage bicycle.

开始日期2013-12-01

申办/合作机构

Rigshospitalet

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100 项与盐酸考尼伐坦相关的临床结果

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100 项与盐酸考尼伐坦相关的转化医学

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100 项与盐酸考尼伐坦相关的专利（医药）

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项与盐酸考尼伐坦相关的文献（医药）

2025-12-01·JOURNAL OF ALZHEIMERS DISEASE

Virtual screening of drugs against multiple targets of Alzheimer's disease

Article

作者: Mesfin, Samuel ; Bloch, Naamah ; Ben Zaken, Karin ; Samson, Abraham O

Background:

Drug repurposing offers a rapid, cost-effective approach for discovering therapies against multiple targets.

Objective:

Here, we screen virtual ligand libraries consisting of 3468 approved drugs against 11 protein targets associated with Alzheimer's disease (AD).

Methods:

We employ blind molecular docking, and target amyloid-β (Aβ), microtubule-associated protein tau (MAPT), Apolipoprotein E4 (APOE4), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid-β protein precursor (AβPP), β-secretase (BACE1), brain-derived neurotrophic factor (BDNF), presenilin 1 (PSEN1) and 2 (PSEN2), and α-synuclein (SNCA) proteins using AutoDock Vina.

Results:

Notably, multitarget binding recurs among the top-10 ligands with Ergotamine and Dihydroergotamine potentially binding 8; Dutasteride 7; Drospirenone and Nilotinib 6; Adapalene and Conivaptan 5; Bromocriptine 4; and Rolapitant, Irinotecan, Plerixafor, Saquinavir, and Telmisartan 3, out of 11 protein targets. As such, we reveal potential binding sites for ergot alkaloids, steroids, retinoids, antivirals, angiotensin receptor blockers, and Neurokinin 1 (NK1) receptor antagonists on multiple AD targets. Importantly, the therapeutic potential of the top-scoring ligands is confounded by pharmacokinetics and adverse-effects. For example, poor blood-brain barrier (BBB) penetration, and vasoconstriction, discount ergot-alkaloid use in AD. Likewise, potential toxicity limits prolonged use of steroids, Nilotinib, Adapalene, and Irinotecan. Conversely, BBB penetration, neuronal protection, oral availability, anti-inflammation, and anti-hypertension, admit Angiotensin receptor blockers (ARB), (Telmisartan/Candesartan); Antidiuretic hormone (ADH) inhibitors (Conivaptan/Tolvaptan); and of the NK1 receptors antagonists (Rolapitant/Netupitant) use in AD.

Conclusions:

Our multitarget screening identifies selective synergistic AD modulators, such as ARB, ADH and NK1 receptor inhibitors, and simplifies drug discovery by focusing on the most promising candidates for experimental validation.

2025-11-07·JOURNAL OF ORGANIC CHEMISTRY

Article

作者: Zhang, Fangjun ; Jiang, Rong ; Zheng, Wenjie ; Yang, Jianing ; Hu, Yuanling ; Xu, Moke ; Shao, Yinlin ; Chen, Wenwen ; Jin, Qian

This investigation presents an innovative methodology for the direct deoxygenative alkenylation of ketones, utilizing pinacolborane as the reducing agent in the presence of the B(C₆F₅)₃ catalyst. A series of aryl ketones containing different functional groups such as hydroxyl, amino, alkynyl, vinyl, and ester groups were found to be well-tolerated. The efficiency of deoxygenative alkenylation could be notably improved by the addition of catalytic LuCl₃ in some substrates. This transformation has also been nicely applied to the gram-scale late-stage functionalization of pharmacologically significant compounds sertraline and conivaptan. Comprehensive mechanistic investigations have elucidated a plausible reaction pathway that proceeds through sequential carbonyl hydroboration, deboration, and deprotonation processes.

2025-11-02·Journal of biomolecular structure & dynamics

Molecular cloning, biophysical and in silico studies of Human papillomavirus 33 E2 DNA binding domain

Article

作者: Nair, Maya S. ; Bharti

Human papillomavirus 33, a high-risk HPV strain, is mainly responsible for HPV infection and cervical cancer in Asian countries. The E2 protein of HPV 33 is a DNA-binding protein that plays a crucial role in viral replication and transcription. We have cloned, overexpressed, and purified the DNA binding domain of the E2 protein. Size exclusion chromatography results suggested that the protein exists in a homodimeric state in the native form. Circular dichroism data showed that the protein has a higher content of β-sheet. The melting temperature obtained from differential scanning calorimetry is 52.59 °C, and the protein is stable at pH 8 and is in a dimeric form at basic pH. The protein is monomeric or unfolded at a very low pH. Chemical denaturation studies suggested that the protein denatured and dissociated simultaneously. The DNA binding activity of the protein was also confirmed and it showed binding affinity in the order of 10⁶ M^-1. The protein structure was modeled using homology modeling and other bioinformatic tools. The virtual screening and molecular dynamic simulation studies were performed to find compounds that can act as potent inhibitors against E2 DBD. This study expands the understanding of the conserved structural and binding properties of HPV33 E2 DBD and provides the first report on the characterization of the viral protein.

项与盐酸考尼伐坦相关的新闻（医药）

2025-12-11

·全球好药资讯

【I/II期临床试验】新一代多靶点抑制剂TL139招募二代ALK抑制剂治疗失败的ALK融合基因阳性非小细胞肺癌患者！

#ALK经治临床试验 #TL139 #韬略生物 #新一代多靶点抑制剂 #二代ALK抑制剂治疗失败的肺癌 #ALK阳性非小细胞肺癌新药临床招募 #NSCLC新药临床招募简要入排本临床药物为口服多靶点酪氨酸激酶抑制剂（TKI）；目前招募ALK融合基因阳性非小细胞肺癌（NSCLC）患者；需要接受过二代ALK抑制剂；排除广泛播散性、双侧或存在3/4级间质性纤维化或间质性肺疾病病史的患者；治疗后稳定4周以上的脑转移患者；全国多中心。研究中心河南郑州浙江杭州北京安徽合肥重庆福建福州广东广州黑龙江哈尔滨湖北武汉湖南长沙江苏南京江西南昌上海山东济南具体启动情况以后期咨询为准【研究中心若有更新请拉至文末查看】试验名称 TL139治疗携带NTRK、ROS1或ALK融合基因阳性的局部晚期或转移性肿瘤患者的I/II期临床试验。试验药物 TL139是一款由苏州韬略生物科技股份有限公司研发的口服多靶点酪氨酸激酶抑制剂（TKI），主要针对NTRK1/2/3、ROS1、ALK及LTK融合基因阳性的局部晚期或转移性实体瘤患者。其作用机制为精准抑制NTRK、ROS1、ALK及LTK融合基因编码的异常酪氨酸激酶活性。这些融合基因是多种实体瘤（如非小细胞肺癌、结直肠癌、乳腺癌等）的驱动因素，异常激活的酪氨酸激酶会持续促进肿瘤细胞增殖、存活及转移。TL139通过阻断这一信号通路，抑制肿瘤生长并诱导其凋亡。研究药物：TL139（I/II期）登记号：CTR20202551 试验类型：单臂试验适应症：ALK融合基因阳性非小细胞肺癌（二线及以上）申办方：苏州韬略生物科技有限公司延伸阅读苏州韬略生物科技股份有限公司 (Teligene Ltd) 是一家以小分子创新药研发和产业化为主的高新医药研发公司。主要瞄准国际新型小分子靶向抗肿瘤药物研发热点及发展趋势，设计、筛选、优化与研发具有自主知识产权的原创小分子靶向抗肿瘤药物。备注：以上信息来源于药企官网注：上下滑动可查看全部内容用药周期 TL139的规格：25mg；用法用量：I期阶段：用法：口服，每日一次或每日两次；用量：起始服药剂量为50mg QD，后续分别为100mg, 125mg和150mg剂量爬坡；II期：将根据I期的数据确定II期给药剂量。用药时程：I期：单次给药，洗脱期7天，后连续给药，每21天为1个周期，直到疾病进展或其他原因停药；II期：连续给药，每21天为1个周期，直到疾病进展或其他原因停药。入选标准 1、年龄≥18周岁，性别不限。 2、经组织学或细胞学确认的局部晚期或转移性NTRK1/2/3、ROS1或ALK 阳性肿瘤患者，之前已通过NGS或核酸类诊断检测方法进行检测确认NTRK1/2/3、ROS1 或 ALK 状态。 3、所有受试者必须至少有根据 RECISTv1.1确定的1处可测量且既往未接受过放疗的颅外靶病变。如果满足以下条件，允许CNS转移：a. 无症状：目前不需要皮质类固醇治疗或剂量稳定或剂量减少≤10mg QD泼尼松或等效药物；或b. 过去诊断，已经完成治疗，入组前放射治疗或手术的急性影响完全恢复，针对这些转移的皮质类固醇治疗至少已经停止4周，且神经系统稳定。 4、受试者应存在以下情况：a.（队列1）ALK阳性，既往接受过≤2种ALK抑制剂的治疗(I期剂量爬坡阶段不允许入初治的患者)。b. （队列2）ROS1阳性，既往接受过≤1种ROS1抑制剂的治疗(I期剂量爬坡阶段不允许入初治的患者)。c. （队列3）NTRK阳性，接受一代NTRK抑制剂（拉罗替尼、恩曲替尼、TL118等）治疗后疾病进展。 5、在研究入组前，接受ALK、ROS1或NTRK抑制剂既往治疗的患者必须完成治疗≥5个半衰期。 6、美国东部肿瘤协作组（ECOG）体能状况评分：0-1。 7、有充分的骨髓、胰腺、肝脏、肾脏和凝血功能：血常规：ANC ≥1.5×10^9/L（1500/mm3），PLT≥90×10^9/L，Hb≥9g/dL（90g/L）（筛查前14天内未输血、未使用造血刺激因子）；胰腺：a. 总血清淀粉酶 ≤1.5×ULN；b. 血清脂肪酶 ≤1.5×ULN。如果总淀粉酶>1.5×ULN，但胰腺淀粉酶在 ULN 范围内，则受试者可以入组。肝脏：a. 血清总胆红素 ≤1.5 x ULN；b. 天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）≤2.5 x ULN（如果肝转移，则≤5.0 x ULN）。肾脏：a. 肌酐清除率≥60mL/min，按Cockcroft and Gault公式计算。 8、既往放疗和化疗的急性影响恢复至基线严重程度或美国国家癌症研究所 (NCI)不良事件通用术语标准（CTCAE）级别1，研究者认为不会对受试者构成安全风险的AE除外。 9、有生育能力的合格受试者（男性和女性）必须同意在试验期间和末次用药后至少6个月（女性）或3个月（男性）内使用可靠的非激素避孕方法（屏障法、节育或禁欲）；育龄期女性受试者入选前7天内的血人绒毛膜促性腺激素（hCG）妊娠检查必须为阴性；男性受试者在首次给药至末次给药后3个月内不能进行精子捐献。 10、所有受试者必须在接受任何本试验规定的检查之前对本研究知情，并自愿签署经伦理委员会批准的书面知情同意书（ICF），并愿意遵循试验治疗方案和访视计划。 11、愿意并能够遵循研究计划的访视、治疗计划、实验室检查和其他程序。排除标准 1、受试者在研究入组前接受的全身抗癌化疗结束时间短于5个药物半衰期。 2、既往接受过特异性针对T细胞共刺激或免疫检查点途径的抗体或药物治疗，包括但不限于抗程序性细胞死亡蛋白1（anti-PD-1）、抗程序性细胞死亡蛋白配体1（anti-PD-L1）、anti-PD-L2、抗分化抗原簇137（anti-CD137）或抗细胞毒性T淋巴细胞相关抗原4（anti-CTLA-4）抗体。 3、受试者在入组前4周内接受大手术。小手术操作（例如输液港植入）不是排除标准，但需要有足够的时间达到伤口充分愈合。 4、受试者在入组前2周内接受放疗。姑息放疗必须在入组前至少48小时完成。立体定向或部分脑部放疗必须在入组前至少2周完成。全脑部放疗必须在入组前至少4周完成。 5、脊髓压迫，除非受试者通过治疗达到良好的疼痛控制，且入组前4周内神经系统功能完全恢复。 6、胃肠道异常，包括不能服用口服药物；需要静脉内营养；既往手术操作影响吸收，包括全胃切除或胃束带手术；活动性炎症性胃肠道疾病、慢性腹泻、症状性憩室病；过去6个月内治疗活动性消化性溃疡疾病；吸收不良综合征。 7、已知既往或怀疑对研究药物或制剂中的任何成分产生重度超敏反应。 8、有临床意义的活动性细菌、真菌或病毒感染，包括乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、已知人类免疫缺陷病毒（HIV）或获得性免疫缺陷综合症（AIDS）相关疾病。 9、有临床意义的心血管疾病（即活动性或入组前3个月内）：脑血管意外/卒中、心肌梗死、不稳定型心绞痛、充血性心力衰竭（纽约心脏协会分类≥II类）、二度或三度房室传导阻滞（除非有起搏器）或任何AV传导阻滞伴PR间期 >220msec；或CTCAE≥2级的持续心律失常，任何等级的未控制心房纤维颤动，心动过缓，定义为<50bpm（除非受试者在其他方面健康，例如长跑运动员等），机器读取ECG QTc >470msec，或先天性长QT综合征，或左心室射血分数＜50%，或未控制的高血压。 10、入组前一个月经研究者判断受试者有急性胰腺炎的易感特征（例如未控制的高血糖、当前胆结石症）。 11、广泛播散性、双侧或存在3/4级间质性纤维化或间质性肺疾病病史，包括肺炎、过敏性肺炎、间质性肺炎、间质性肺疾病、闭塞性细支气管炎和肺纤维化。 12、在入组前过去3年内活动性恶性肿瘤的证据（除了NSCLC、NTRK融合基因阳性肿瘤，非黑色素瘤皮肤癌、原位宫颈癌、甲状腺乳头状癌、小叶原位癌（LCIS）/导管原位癌（DCIS）或局部且推测已痊愈的前列腺癌）。 13、在给药前12天内伴随使用下列任何食物或药物（如果怀疑食物或药物是否属于上述任何类别，请向申办方咨询）：a. 已知强CYP3A抑制剂（例如阿扎那韦、波西普韦、克拉霉素、考尼伐坦、茚地那韦、伊曲康唑、酮康唑、洛匹那韦、咪拉地尔、奈法唑酮、奈非那韦、泊沙康唑、利托那韦、沙奎那韦、特拉匹韦、泰利霉素、三乙酰竹桃霉素、伏立康唑、葡萄柚汁或葡萄柚/葡萄柚相关柑橘类水果[例如酸橙、柚子]）。允许局部使用这些药物（如适用），例如2%酮康唑乳膏；b. 已知强CYP3A诱导剂（例如阿伐麦布、卡马西平、苯巴比妥、苯妥英、利福布汀、利福平、圣约翰草）；疑似具有CYP3A4诱导效应的伴随用药必须得到申办方的批准；c. 治疗指数窄的已知P-糖蛋白（P-gp）底物（例如地高辛）。 14、在研究用药品给药时，无法停止伴随使用治疗指数窄的CYP3A底物（如果怀疑食物或药物是否属于上述任何类别，请向申办方咨询）（例如阿芬太尼、阿司咪唑、西沙必利、环孢菌素、二氢麦角胺、麦角胺、芬太尼、包括透皮贴剂、匹莫齐特、奎尼丁、西罗莫司、他克莫司、特非那丁）。 15、可能增加与研究参与或研究药品使用有关的风险，或者可能干扰研究结果判读和（根据研究者判断）可能使受试者不适合参加本研究的其他严重急性或慢性医学或精神疾病（包括近期[过去一年内]或活跃的自杀意念或行为）或者实验室检查异常。 16、入组研究前2周内和/或在研究期间参加涉及研究性药物的其他研究。 17、有其它严重（NCI CTCAE v5.0严重程度评价≥3级）的系统性疾病史，经研究者判断不适合参加临床试验。 18、已知有酒精或药物依赖。更多项目信息请参考： http://www.chinadrugtrials.org.cn/index.html 温馨提示：文章入排信息来源于国家临床试验官网公示信息，具体情况以实际咨询为准！报名方式参与临床试验，获取国际前沿新药新疗法使用机会！更有一线专家团队为你的治疗保驾护航！【印塔健康】目前有肺癌、肝癌、肾癌、胃癌、肠癌、胰腺癌、妇瘤、泌尿肿瘤、血液肿瘤......等几乎涵盖所有癌种的临床试验正在招募患者！扫描下方二维码添加医学运营一对一咨询或点击左下角“阅读原文”直接报名！我们将会在24小时内（工作日）与您电话或微信联系，请保持手机畅通！【重要提示】印塔健康旗下公众号【全球好药资讯】所有文章信息仅供参考，具体治疗谨遵医嘱！ HJ-004-02招募非鳞非小细胞肺癌 ENPP1抑制剂ZX-8177招募实体瘤 ADC新药注射用HDM2017招募实体瘤笑对人生不负所爱

2025-12-08

·investor.cumberlandpharma.com

CALDOLOR® (IBUPROFEN) INJECTION CMS ISSUED J-CODE NOW ASSOCIATED WITH REIMBURSEMENT PRICE SUPPORTING NON-OPIOID PAIN MANAGEMENT

NASHVILLE, Tenn. , Dec. 8, 2025 /PRNewswire/ -- Cumberland Pharmaceuticals Inc. (Nasdaq: CPIX), today announced an important update regarding its Caldolor® (ibuprofen) Injection. The product's permanent J-code, J1741, is now officially associated with a reimbursement price, providing healthcare providers with a CMS-covered, non-opioid option for managing pain and fever. As the nation continues to face an opioid crisis, non-opioid alternatives, like Caldolor, play a critical role in reducing reliance on opioid medications, supporting safer pain management strategies for patients. With the reimbursement price now linked to J1741, providers can access a CMS-covered, non-opioid pain management option and align treatment strategies with opioid-sparing initiatives. Caldolor J-Code Details: Product: Caldolor® (ibuprofen) Injection J-Code: J1741 – Injection, ibuprofen, 100 mg Status: Now associated with reimbursement price "With Caldolor now linked to an established reimbursement price, healthcare providers have a reimbursable non-opioid alternative to help address pain management," said Cumberland Pharmaceuticals CEO A.J. Kazimi . "This update supports providers in making clinically appropriate decisions while contributing to efforts to reduce opioid exposure and reinforces our commitment to improving access to Caldolor and ensuring patients receive the pain management they need." Providers are encouraged to update their internal systems, billing teams, and reimbursement processes to reflect this change. For additional support with coding, coverage, or payment questions, please contact your Cumberland Pharmaceuticals representative or email caldolor@cumberlandpharma.com. About Caldolor® (ibuprofen) Injection Caldolor is indicated in adults and pediatric patients for the management of mild to moderate pain and management of moderate to severe pain as an adjunct to opioid analgesics, as well as the reduction of fever. It was the first FDA-approved intravenous therapy for fever. Caldolor is contraindicated in patients with known hypersensitivity to ibuprofen or other NSAIDs, patients with a history of asthma or other allergic type reactions after taking aspirin or other NSAIDs. Caldolor is contraindicated for use during the peri-operative period in the setting of coronary artery bypass graft (CABG) surgery. For full prescribing and safety information, including boxed warning, visit www.caldolor.com. About Cumberland Pharmaceuticals Cumberland Pharmaceuticals Inc. is the largest biopharmaceutical company founded and headquartered in Tennessee and is focused on providing unique products that improve the quality of patient care. The company develops, acquires, and commercializes products for the hospital acute care, gastroenterology and oncology market segments. The company's portfolio of FDA-approved brands includes: Acetadote® (acetylcysteine) injection, for the treatment of acetaminophen poisoning; Caldolor® (ibuprofen) injection, for the treatment of pain and fever; Kristalose® (lactulose) oral, a prescription laxative, for the treatment of constipation; Sancuso® (granisetron) transdermal, for the prevention of nausea and vomiting in patients receiving certain types of chemotherapy treatment; Vaprisol® (conivaptan) injection, to raise serum sodium levels in hospitalized patients with euvolemic and hypervolemic hyponatremia; Vibativ® (telavancin) injection, for the treatment of certain serious bacterial infections including hospital-acquired and ventilator-associated bacterial pneumonia, as well as complicated skin and skin structure infections, and Talicia®(omeprazole magnesium, amoxicillin and rifabutin) oral capsule, for the treatment of H. pylori infection. The company also has a series of Phase II clinical programs underway evaluating its ifetroban product candidate in patients with cardiomyopathy associated with Duchenne Muscular Dystrophy, Systemic Sclerosis and Idiopathic Pulmonary Fibrosis. For more information on Cumberland's approved products, including full prescribing information, please visit links to the individual product websites, which can be found on the company's website www.cumberlandpharma.com. Forward-Looking Statements This press release contains forward-looking statements, which are subject to certain risks and reflect Cumberland's current views on future events based on what it believes are reasonable assumptions. No assurance can be given that these events will occur. As with any business, all phases of Cumberland's operations are subject to factors outside of its control, and any one or combination of these factors could materially affect Cumberland's results of operations. These factors include market conditions, competition, an inability of manufacturers to produce Cumberland's products on a timely basis or failure of manufacturers to comply with regulations applicable to pharmaceutical manufacturers, maintaining an effective sales and marketing infrastructure, natural disasters, public health epidemics, and other events beyond our control, as more fully discussed in the Company's most recent Form 10-K and subsequent 10-Qs as filed with the SEC . There can be no assurance that results anticipated by the Company will be realized or that they will have the expected effects. Readers are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date hereof. The Company does not undertake any obligation to publicly revise these statements to reflect events after the date hereof. View original content:https://www.prnewswire.com/news-releases/caldolor-ibuprofen-injection-cms-issued-j-code-now-associated-with-reimbursement-price-supporting-non-opioid-pain-management-302634989.html SOURCE Cumberland Pharmaceuticals Inc. CONTACTS: Investor Contact: Shayla Simpson, Cumberland Pharmaceuticals Inc., (615) 255-0068; Media Contact: Emily Kent, Dalton Agency, (540) 621-5448

上市批准临床2期

2025-11-08

·BioArt

Nat Commun丨蒋轶/郭栋/徐华强合作破解水盐平衡调控密码

人体内水分约占体重的70%，维持精准的水盐平衡对生命健康至关重要。作为调控水盐平衡的“核心开关”，血管加压素V2受体（Vasopressin 2 receptor, V2R）不仅掌管着水分的重吸收，更是治疗低钠血症、尿崩症和心衰水肿等疾病的重要药物靶点。然而，目前临床使用的V2R拮抗类药物存在明显局限：托伐普坦潜藏肝毒性风险，考尼伐普坦则因同时作用于该家族其他亚型V1aR而缺乏精准靶向性。在前期成功揭示内源性多肽精氨酸加压素（AVP）识别并激活V2R机制的基础上（Cell Research，2021），近日，临港实验室蒋轶团队联合徐州医科大学郭栋团队和中国科学院上海药物研究所徐华强团队，共同解析了V2R分别与两种临床拮抗药物——托伐普坦和考尼伐坦结合的高分辨率冷冻电镜结构（图1）。该研究揭示了V2R识别拮抗剂的精细分子机制，为开发新一代靶向V2R的药物奠定了关键结构基础，该研究成果于2025年11月4日发表于Nature Communications杂志，题为：Structural insights into antagonist recognition by the vasopressin V2 receptor。图1. V2R与托伐普坦及考尼伐坦结合的冷冻电镜结构研究发现，托伐普坦和考尼伐坦在V2R的正构结合口袋中呈现出截然不同的结合模式。托伐普坦以“深度插入”的方式占据口袋，其苯并氮䓬基团（A 区）和甲基苯基基团（B 区）与V2R的TM3、TM5和TM6等区域的疏水残基形成稳定相互作用，同时通过氢键进一步增强结合稳定性（图2）。图2. 托伐普坦与V2R的识别机制与托伐普坦不同的是，考尼伐普坦以“浅层结合”的方式存在于V2R口袋中。其苯并咪唑并氮䓬基团（A 区）靠近托伐普坦的对应区域，但苯环（B 区）和联苯（C 区）则朝向细胞外环 1（ECL1），且联苯基团与ECL1的F105残基形成π-π相互作用，这一独特作用对考尼伐坦的活性至关重要（图3）。图3. 考尼伐普坦与V2R的识别机制研究团队进一步发现了一种依赖TM7螺旋构象的V2R拮抗机制。在活性状态下，血管加压素（Vasopressin, AVP）与V2R结合会导致TM7特定区域螺旋结构扭曲，从而激活受体；而拮抗剂结合后，可通过占据正构结合口袋，空间上阻碍AVP与TM7关键区域的相互作用，维持TM7螺旋的连续性，阻止其发生激活所需的构象变化，进而抑制受体激活（图4）。这一发现为深入理解GPCR家族的功能多样性提供了新视角。图4. 非活性托伐普坦-V2R与活性AVP-V2R复合物的结构对比该研究成果不仅深化了我们对人体水盐平衡调控机制的理解，更为设计更安全、高效、高选择性的新一代V2R拮抗剂奠定了关键结构基础，有望突破现有药物研发瓶颈，最终为水盐平衡紊乱类疾病提供更优的治疗方案。临港实验室蒋轶研究员、徐州医科大学郭栋教授和中国科学院上海药物研究所徐华强研究员为该研究的共同通讯作者，临港实验室与上海科技大学联合培养博士生章天炜、徐州医科大学刘宏丽副教授和中国科学院上海药物研究所游宠昭博士为该论文的共同第一作者全文链接：https://doi.org/10.1038/s41467-025-64735-x 制版人：十一学术合作组织（*排名不分先后）战略合作伙伴（*排名不分先后） · 转载须知【非原创文章】本文著作权归文章作者所有，欢迎个人转发分享，未经作者的允许禁止转载，作者拥有所有法定权利，违者必究。 BioArt Med Plants 人才招聘近期直播推荐点击主页推荐活动关注更多最新活动！

100 项与盐酸考尼伐坦相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01236	盐酸考尼伐坦	C03XA02	DB00872

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
心脏衰竭	美国	Cumberland Pharmaceuticals, Inc.	2005-12-29
低钠血症	美国	Cumberland Pharmaceuticals, Inc.	2005-12-29

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
急性失代偿性心力衰竭	临床3期	印度	Cumberland Pharmaceuticals, Inc.	2009-04-01
慢性低钠血症	临床2期	中国	北京福瑞康正医药技术研究所	2018-08-28
慢性低钠血症	临床2期	中国	江苏万高药业股份有限公司	2018-08-28
水中毒	临床2期	中国	江苏万高药业股份有限公司	2018-08-28
水中毒	临床2期	中国	北京福瑞康正医药技术研究所	2018-08-28
慢性心力衰竭	临床2期	美国	Cumberland Pharmaceuticals, Inc.	2002-11-01
失代偿性慢性心力衰竭	临床2期	美国	Cumberland Pharmaceuticals, Inc.	2002-11-01
肾脏疾病	临床1期	美国	Cumberland Pharmaceuticals, Inc.	2009-04-01
慢性充血性心力衰竭	临床阶段不明	美国	Astellas Pharma, Inc.	2009-07-01
类鼻疽	临床前	印度	Indian Institute of Technology Kharagpur	2025-05-18

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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


NCT03000283 (CTgov)	临床1期	脑出血 \| 脑卒中 \| 脑水肿	7	Conivaptan	積淵淵網鏇餘衊獵鏇範 = 顧鏇顧範繭繭艱膚艱顧齋襯繭壓積網淵壓鬱鹽 (壓醖積糧齋積艱獵餘齋, 鏇顧餘製淵範蓋憲艱遞 ~ 憲餘選積製製夢醖衊醖) 更多	-	2020-04-17
NCT01451411 (CTgov)	临床3期	低钠血症	4	Conivaptan hydrochloride (Conivaptan Hydrochloride)	選獵願壓鹹選網餘醖夢(憲獵糧繭選構餘膚遞鏇) = 觸衊夢鹽願壓築壓鬱遞齋醖廠壓顧範願顧願衊 (淵繭範簾積選網廠憲憲, 5.3) 更多	-	2016-03-01
				Placebo (Placebo)	選獵願壓鹹選網餘醖夢(憲獵糧繭選構餘膚遞鏇) = 顧鹹鑰糧遞壓鹽糧繭範齋醖廠壓顧範願顧願衊更多
NCT00843986 (CONVERT-H, CTgov)	临床3期	低钠血症 \| 急性失代偿性心力衰竭	9	placebo (Placebo)	襯艱襯鏇餘蓋壓獵顧構(鹹鹽積遞鹹觸獵壓廠範) = 顧顧築觸艱獵願鬱鑰網鑰鹽選蓋簾鏇顧鹹夢遞 (製餘壓齋窪鏇簾鹹簾簾, 獵憲範鹽繭簾齋窪艱鬱 ~ 廠鏇餘範簾構積選簾範) 更多	-	2010-10-01
				conivaptan (Conivaptan)	襯艱襯鏇餘蓋壓獵顧構(鹹鹽積遞鹹觸獵壓廠範) = 淵顧窪鹹築遞鹽製壓顧鑰鹽選蓋簾鏇顧鹹夢遞 (製餘壓齋窪鏇簾鹹簾簾, 積夢製蓋遞鹹窪膚鏇鬱 ~ 遞鏇製鹹膚鏇鹹淵糧顧) 更多
NCT00592475 (CTgov)	临床2期	-	20	conivaptan (Regimen 1 Conivaptan 12.5 mg)	憲顧鹽鹹築壓膚衊蓋餘(壓鬱簾餘鏇糧繭膚願夢) = 選淵願鑰壓顧獵餘窪選壓壓鑰醖範鏇願積齋醖 (鏇鹹選簾願積築襯窪願, 4.375) 更多	-	2010-09-28
				conivaptan (Regimen 2 Conivaptan 25 mg)	憲顧鹽鹹築壓膚衊蓋餘(壓鬱簾餘鏇糧繭膚願夢) = 夢範夢膚衊窪衊簾範構壓壓鑰醖範鏇願積齋醖 (鏇鹹選簾願積築襯窪願, 4.750) 更多
NCT00435591 (CTgov)	临床4期	低钠血症	121	placebo+Conivaptan (Dose Regimen 1)	選蓋蓋膚糧繭襯繭範積 = 壓築餘遞齋艱積鹽網襯簾製構構遞鑰築膚夢衊 (觸網觸遞繭繭憲鹽壓糧, 廠遞壓繭願蓋夢網醖選 ~ 遞糧製遞蓋範製範網築) 更多	-	2010-05-26
				Conivaptan (Dose Regimen 2)	選蓋蓋膚糧繭襯繭範積 = 淵積糧淵鏇製衊遞鹹鹽簾製構構遞鑰築膚夢衊 (觸網觸遞繭繭憲鹽壓糧, 壓獵網糧鹹廠餘築蓋選 ~ 淵艱齋齋艱鹹壓構製艱) 更多
NCT00478192 (CTgov)	临床3期	低钠血症	50	Conivaptan (Regimen 1 Conivaptan QD)	選餘醖壓選獵蓋夢衊襯(顧壓淵壓鏇鑰積膚蓋簾) = 襯積觸醖餘築願壓膚鑰範鏇鹹構廠淵膚範鹹衊 (簾願積齋鑰簾醖積範壓, 4.017) 更多	-	2010-04-21
				Conivaptan (Regimen 2 Conivaptan BID)	選餘醖壓選獵蓋夢衊襯(顧壓淵壓鏇鑰積膚蓋簾) = 鏇顧顧獵顧鏇鏇鏇製鏇範鏇鹹構廠淵膚範鹹衊 (簾願積齋鑰簾醖積範壓, 3.581) 更多