Cobiprostone(Cobiprostone) - 药物靶点：CLCN2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Cobiprostone (USAN)

靶点

CLCN2

作用方式

激动剂

作用机制

CLCN2激动剂(氯离子通道蛋白2激动剂)

治疗领域

肿瘤免疫系统疾病消化系统疾病+ [5]

在研适应症-

非在研适应症

头颈部肿瘤门静脉高血压炎症性肠病+ [9]

原研机构

Sucampo Pharmaceuticals LLC

在研机构-

非在研机构

Sucampo Pharmaceuticals LLC

基亚生物科技股份有限公司Sucampo Pharma Americas LLC

权益机构-

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C21H34F2O5

InChIKeySDDSJMXGJNWMJY-BRHAQHMBSA-N

CAS号333963-42-1

关联

5

项与 Cobiprostone 相关的临床试验

NCT02542215

/ Terminated临床2期

A Multicenter, Randomized, Placebo-controlled, Double-blinded Study of the Efficacy, Safety, and Pharmacokinetics of Cobiprostone for the Prevention of Severe Oral Mucositis in Subjects With Head and Neck Cancer (HNC)

Treatment for head and neck cancer often involves a combination of chemotherapy and radiation.
One of the unfortunate consequences of standard care for head and neck cancer is the development of painful mouth sores, known as oral mucositis.
This study will evaluate the use of cobiprostone spray to prevent oral mucositis, when given for the duration of radiation and chemotherapy (RT/CT) standard care.

开始日期2015-06-01

申办/合作机构

Sucampo Pharma Americas LLC

JPRN-jRCT2080222711

/ Unknown status临床2期

A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of SPI-8811 Oral Solution in Patients With Non-erosive Reflux Disease (NERD) Refractory to Proton Pump Inhibitors

开始日期2014-12-26

申办/合作机构

Sucampo Pharma LLC

NCT00737594

/ Terminated临床2期

A Randomized, Placebo-controlled, Double-blinded Study of the Efficacy and Safety of Cobiprostone in Patients With Portal Hypertension

The primary purpose of this study is to determine the efficacy and safety of cobiprostone (at two dose levels) as compared to placebo for lowering portal hypertension.

开始日期2008-07-01

申办/合作机构

Sucampo Pharma Americas LLC

[+1]

100 项与 Cobiprostone 相关的临床结果

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100 项与 Cobiprostone 相关的转化医学

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100 项与 Cobiprostone 相关的专利（医药）

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2

项与 Cobiprostone 相关的文献（医药）

2017-06-01·American Journal of Physiology-Cell Physiology3区 · 生物学

Identification of the fatty acid activation site on human ClC-2

3区 · 生物学

Article

作者: Chakrabarti, Jayati ; Malinowska, Danuta H. ; Cuppoletti, John ; Tewari, Kirti P.

Fatty acids (including lubiprostone and cobiprostone) are human ClC-2 (hClC-2) Cl− channel activators. Molecular and cellular mechanisms underlying this activation were examined. Role of a four-amino acid PKA activation site, RGET691, of hClC-2 was investigated using wild-type (WT) and mutant (AGET, RGEA, and AGAA) hClC-2 expressed in 293EBNA cells as well as involvement of PKA, intracellular cAMP concentration ([cAMP]i), EP2, or EP4 receptor agonist activity. All fatty acids [lubiprostone, cobiprostone, eicosatetraynoic acid (ETYA), oleic acid, and elaidic acid] caused significant rightward shifts in concentration-dependent Cl− current activation (increasing EC50s) with mutant compared with WT hClC-2 channels, without changing time and voltage dependence, current-voltage rectification, or methadone inhibition of the channel. As with lubiprostone, cobiprostone activation of hClC-2 occurred with PKA inhibitor (myristoylated protein kinase inhibitor) present or when using double PKA activation site (RRAA655/RGEA691) mutant. Cobiprostone did not activate human CFTR. Fatty acids did not increase [cAMP]i in hClC-2/293EBNA or T84 cells. Using T84 CFTR knockdown cells, cobiprostone increased hClC-2 Cl− currents without increasing [cAMP]i, while PGE2 and forskolin-IBMX increased both. Fatty acids were not agonists of EP2 or EP4 receptors. L-161,982, a supposed EP4-selective inhibitor, had no effect on lubiprostone-activated hClC-2 Cl− currents but significantly decreased T84 cell barrier function measured by transepithelial resistance and fluorescent dextran transepithelial movement. The present findings show that RGET691 of hClC-2 (possible binding site) plays an important functional role in fatty acid activation of hClC-2. PKA, [cAMP]i, and EP2 or EP4 receptors are not involved. These studies provide the molecular basis for fatty acid regulation of hClC-2.

2012-01-01·World Journal of Gastroenterology3区 · 医学

Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa

3区 · 医学

Article

作者: Ryuji Ueno ; Adam Moeser ; Anthony Blikslager ; Meghali Nighot

AIMTo evaluate the protective properties of novel prostone ClC-2 agonist SPI-8811 in porcine model of gastric acid injury.METHODSPorcine gastric mucosa was mounted in Ussing chambers and injured by bathing mucosal tissues in an HCl Ringer's solution (pH = 1.5) with or without SP1-8811 (1 μmol/L), cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor (inhibitor 172, 10 μmol/L, apical) and ClC-2 inhibitor ZnCl₂, 300 μmol/L, apical), on the apical surface of tissues. Transepithelial resistance and mucosal-to-serosal ³H-mannitol fluxes were measured over a 90-min period. Tissues were analyzed by morph metric techniques, Immunofluorescence and by western blots.RESULTSCompared with control tissues, acid exposure decreased transepithelial electrical resistance (TER) and increased ³H-mannitol flux. Pretreatment of gastric mucosa with SPI-8811 was protective against acid-induced decreases in TER (TER, 50 Ω.cm² vs 100 Ω.cm²) and abolished increases in flux (³H-mannitol flux, 0.10 μmol/L.cm² vs 0.04 μmol/L.cm²). Evidence of histological damage in the presence of acid was markedly attenuated by SPI-0811. Immunofluorescence and western analysis for occludin revealed enhanced localization to the region of the tight junction (TJ) after treatment with SPI-8811. Pretreatment with the ClC-2 inhibitor ZnCl₂, but not the selective CFTR inhibitor 172, attenuated SPI-8811-mediated mucosal protection, suggesting a role for ClC-2. Prostone may serve both protective and reparative roles in injured tissues.CONCLUSIONClC-2 agonist SPI-8811 stimulated enhancement of mucosal barrier function by protecting TJ protein occludin in porcine gastric mucosa and thus protected the gastric acid injury in porcine stomach.

100 项与 Cobiprostone 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08893	-	-	DB05514

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
头颈部肿瘤	临床2期	美国	Sucampo Pharma Americas LLC	2015-06-01
口腔炎	临床2期	美国	Sucampo Pharma Americas LLC	2015-06-01
非糜烂性反流病	临床2期	-	Sucampo Pharmaceuticals LLC	2014-12-26
门静脉高血压	临床2期	美国	Sucampo Pharma Americas LLC	2008-07-01
骨关节炎	临床2期	美国	Sucampo Pharma Americas LLC	2007-08-01
类风湿关节炎	临床2期	美国	Sucampo Pharma Americas LLC	2007-08-01
溃疡	临床2期	美国	Sucampo Pharma Americas LLC	2007-08-01
黑色素瘤	临床2期	美国	基亚生物科技股份有限公司	2005-06-01
黑色素瘤	临床2期	澳大利亚	基亚生物科技股份有限公司	2005-06-01
非酒精性脂肪性肝炎	临床2期	美国	Sucampo Pharmaceuticals LLC	-

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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


NCT00597818 (CTgov)	临床2期	骨关节炎 \| 溃疡 \| 类风湿关节炎	121	Placebo (Placebo)	顧壓製廠鑰鑰選築鑰衊(選憲鏇獵夢淵範蓋醖餘) = 遞繭糧襯網醖選糧夢艱獵範壓積觸蓋壓齋簾艱 (窪範衊壓觸鏇顧觸鹹鬱, 齋衊餘獵鹹鹹衊遞鬱鏇 ~ 衊糧觸鏇壓鬱獵鏇夢選) 更多	-	2019-12-26
				Non-steroidal anti-inflammatory drug+Cobiprostone (Cobiprostone QD)	顧壓製廠鑰鑰選築鑰衊(選憲鏇獵夢淵範蓋醖餘) = 艱選積觸糧獵簾淵繭壓獵範壓積觸蓋壓齋簾艱 (窪範衊壓觸鏇顧觸鹹鬱, 鏇醖壓製壓遞鑰鹽衊餘 ~ 鬱鹹齋鬱糧憲構遞鬱襯) 更多
NCT00737594 (CTgov)	临床2期	门静脉高血压	9	Cobiprostone (12 mcg TID)	鹹蓋艱憲鏇憲襯淵窪築(餘積鬱製製憲醖積糧製) = 製製選淵網夢淵築壓鑰鏇繭餘鬱衊憲觸獵醖糧 (蓋製窪網築糧顧餘獵製, 繭膚簾淵築範築鹽範鹹 ~ 鏇壓齋壓繭壓網鏇網選) 更多	-	2016-03-16
				Cobiprostone (18 mcg TID)	鹹蓋艱憲鏇憲襯淵窪築(餘積鬱製製憲醖積糧製) = 襯鑰遞鹽壓壓遞膚鬱積鏇繭餘鬱衊憲觸獵醖糧 (蓋製窪網築糧顧餘獵製, 網範願鹹製鹽夢艱壓齋 ~ 淵醖餘餘餘鹹願網獵窪) 更多