Catalog No.S1675 Synonyms: RU 0211
Molecular Weight(MW): 390.46
Lubiprostone is an activator of ClC-2 chloride channels, used in the management of idiopathic chronic constipation.
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|Description||Lubiprostone is an activator of ClC-2 chloride channels, used in the management of idiopathic chronic constipation.|
Lubiprostone induces a robust secretory response in T84 monolayers. Lubiprostone induces a rise in cAMP levels that was sensitive to EP(4)-receptor blockage in T84 cells.  Lubiprostone induces a contraction in rat and human stomach longitudinal muscle, which is inhibited by pretreatment with the EP(1) receptor antagonist but not by the EP(3) or EP(4) receptor antagonists. Lubiprostone also reduces electrically stimulated, neuronal contractions in rat and human colon circular muscle preparations.  Lubiprostone (1 mM) stimulates higher elevations in TER despite lower I(sc) responses compared with the nonselective secretory agonist PGE(2) (1 mM). Lubiprostone significantly reduces mucosal-to-serosal fluxes of (3)H-labeled mannitol to levels comparable to those of normal control tissues and restored occludin localization to tight junctions.  Lubiprostone causes comparable and maximal increases of I(sc) in T84 cells. Lubiprostone-induced increases in iodide efflux are ~80% of those obtained with forskolin. Lubiprostone activates Cl(-) secretion in T84 cells via cAMP, protein kinase A, and by increasing apical membrane CFTR protein.  Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evokes increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1-3000 nM evokes increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. 
|In vivo||Lubiprostone induces a CdCl(2)-insensitive secretory response in mouse intestine, but fail to induce intestinal Cl(-) secretion in Cftr-null mice. |
-  Bijvelds MJ, et al. Gastroenterology, 2009, 137(3), 976-985.
-  Bassil AK, et al. Br J Pharmacol, 2008, 154(1), 126-135.
-  Moeser AJ, et al. Am J Physiol Gastrointest Liver Physiol, 2007, 292(2), G647-656.
|In vitro||DMSO||78 mg/mL (199.76 mM)|
|Ethanol||78 mg/mL (199.76 mM)|
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Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT03097861||Completed||Drug: Lubiprostone|Drug: Placebo||Chronic Idiopathic Constipation||Sucampo AG|Sucampo Pharmaceuticals Inc.|Takeda|Sucampo Pharma Americas LLC||February 13 2017||Phase 3|
|NCT01469819||Completed||Drug: Lubiprostone||Chronic Idiopathic Constipation||Texas Tech University Health Sciences Center El Paso|Takeda Pharmaceuticals North America Inc.||June 2012||Phase 2|Phase 3|
|NCT01324284||Completed||Drug: Lubiprostone||Colorectal Carcinoma||Asian Institute of Gastroenterology India||March 2011||Phase 3|
|NCT00934479||Completed||Drug: Lubiprostone||Other Constipation|Irritable Bowel Syndrome||Mayo Clinic|Arizona State University|Takeda Pharmaceuticals North America Inc.||April 2010||Phase 1|
|NCT01085643||Completed||Drug: Lubiprostone|Drug: Placebo||Constipation-predominant Irritable Bowel Syndrome||Cedars-Sinai Medical Center|Takeda Pharmaceuticals North America Inc.||March 2010||Not Applicable|
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