Delving into the Latest Updates on Cobiprostone with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Cobiprostone (USAN)

Target

CLCN2

Mechanism

CLCN2 agonists(Chloride channel protein 2 agonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [5]

Active Indication-

Inactive Indication

Head and Neck NeoplasmsHypertension, PortalInflammatory Bowel Diseases+ [9]

Originator Organization

Sucampo Pharmaceuticals LLC

Active Organization-

Inactive Organization

Sucampo Pharmaceuticals LLC

Medigen Biotechnology Corp.Sucampo Pharma Americas LLC

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC21H34F2O5

InChIKeySDDSJMXGJNWMJY-BRHAQHMBSA-N

CAS Registry333963-42-1

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.

Start Date01 Jun 2015

Sponsor / Collaborator

Sucampo Pharma Americas LLC

JPRN-jRCT2080222711

/ Unknown statusPhase 2

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

Start Date26 Dec 2014

Sponsor / Collaborator

Sucampo Pharma LLC

NCT00737594

/ TerminatedPhase 2

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.

Start Date01 Jul 2008

Sponsor / Collaborator

Sucampo Pharma Americas LLC

[+1]

100 Clinical Results associated with Cobiprostone

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100 Translational Medicine associated with Cobiprostone

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100 Patents (Medical) associated with Cobiprostone

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2

Literatures (Medical) associated with Cobiprostone

01 Jun 2017·American Journal of Physiology-Cell PhysiologyQ3 · BIOLOGY

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

Q3 · BIOLOGY

Article

Author: 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.

01 Jan 2012·World Journal of GastroenterologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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 Deals associated with Cobiprostone

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External Link

KEGG	Wiki	ATC	Drug Bank
D08893	-	-	DB05514

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Head and Neck Neoplasms	Phase 2	US	Sucampo Pharma Americas LLC	01 Jun 2015
Stomatitis	Phase 2	US	Sucampo Pharma Americas LLC	01 Jun 2015
Non-erosive reflux disease	Phase 2	-	Sucampo Pharmaceuticals LLC	26 Dec 2014
Hypertension, Portal	Phase 2	US	Sucampo Pharma Americas LLC	01 Jul 2008
Osteoarthritis	Phase 2	US	Sucampo Pharma Americas LLC	01 Aug 2007
Rheumatoid Arthritis	Phase 2	US	Sucampo Pharma Americas LLC	01 Aug 2007
Ulcer	Phase 2	US	Sucampo Pharma Americas LLC	01 Aug 2007
Melanoma	Phase 2	US	Medigen Biotechnology Corp.	01 Jun 2005
Melanoma	Phase 2	AU	Medigen Biotechnology Corp.	01 Jun 2005
Nonalcoholic Steatohepatitis	Phase 2	US	Sucampo Pharmaceuticals LLC	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00597818 (CTgov)	Phase 2	Osteoarthritis \| Ulcer \| Rheumatoid Arthritis	121	Placebo (Placebo)	nemeuhsgtt(uolhymqupa) = mjkwqgizqa aulpybcgho (acbvkdamdb, uqotnmknjm - hssyidoqsl) View more	-	26 Dec 2019
				Non-steroidal anti-inflammatory drug+Cobiprostone (Cobiprostone QD)	nemeuhsgtt(uolhymqupa) = cczrhraqob aulpybcgho (acbvkdamdb, oqozfjmkqq - zpmfycnlnq) View more
NCT00737594 (CTgov)	Phase 2	Hypertension, Portal	9	Cobiprostone (12 mcg TID)	tfrdvpnakb(tyotngczhm) = hbkipkhrku dkhnvhttwe (aulrlublgc, zfesauxnny - jltewcoxva) View more	-	16 Mar 2016
				Cobiprostone (18 mcg TID)	tfrdvpnakb(tyotngczhm) = xzjlwcqljj dkhnvhttwe (aulrlublgc, orihdqjifw - tednsojtbg) View more