Investigational Drug Details
| Drug ID: | D212 |
| Drug Name: | Lubiprostone |
| Synonyms: | Lubiprostone |
| Type: | Chemical drug |
| DrugBank ID: | DB01046 |
| DrugBank Description: | Lubiprostone is a medication used in the management of idiopathic chronic constipation. A prostaglandin E1 derivative, lubiprostone is a bicyclic fatty acid that activates ClC-2 chloride channels located on the apical side of the gastrointestinal epithelial cells. Activation of these channels promotes the secretion of a chloride-rich fluid that soften the stool, increase gastrointestinal motility, and induce spontaneous bowel movements (SBM). |
| PubChem ID: | 157920 |
| CasNo: | 333963-40-9, 136790-76-6 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C(CCCC)(F)(F)[C@]1(O)O[C@H]2[C@H](CC1)[C@H](C(=O)C2)CCCCCCC(=O)O |
| Structure: |
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| InChiKey: | WGFOBBZOWHGYQH-MXHNKVEKSA-N |
| Molecular Weight: | 390.467 |
| DrugBank Targets: | Chloride channel protein 2 inducer |
| DrugBank MoA: | Lubiprostone acts by specifically activating ClC-2 chloride channels, which is a normal constituent of the apical membrane of the human intestine, in a protein kinase A action independent fashion. Activation of ClC-2 chloride channels causes an efflux of chloride ions into the lumen, which in turn leads to an efflux of sodium ions through a paracellular pathway to maintain isoelectric neutrality. As a result, water follows sodium into the lumen in order to maintain isotonic equilibrium, thereby increasing intestinal fluid secretion. By increasing intestinal fluid secretion, lubiprostone increases motility in the intestine, thereby increasing the passage of stool and alleviating symptoms associated with chronic idiopathic constipation. Activation of ClC-2 chloride channels may also stimulate the recovery of muscosal barrier function by restoring tight junction protein complexes in the intestine. Patch clamp cell studies in human cell lines have indicated that the majority of the beneficial biological activity of lubiprostone and its metabolites is observed only on the apical (luminal) portion of the gastrointestinal epithelium. |
| DrugBank Pharmacology: | Chronic idiopathic constipation is generally defined by infrequent or difficult passage of stool. The signs and symptoms associated with chronic idiopathic constipation (i.e., abdominal pain or discomfort, bloating, straining, and hard or lumpy stools) may be the result of abnormal colonic motility that can delay the transit of intestinal contents and impede the evacuation of rectal contents. One approach to the treatment of chronic idiopathic constipation is the secretion of fluid into the abdominal lumen through the activation of chloride channels in the apical membrane of the gastrointestinal epithelium. Lubiprostone is a locally acting chloride channel activator that increases intestinal chloride and fluid secretion without altering sodium and potassium concentrations in the serum. |
| DrugBank Indication: | For the treatment of chronic idiopathic constipation in the adult population. Also used for the treatment of irritable bowel syndrome with constipation in women who are 18 years of age or older. |
| Targets: | -- |
| Therapeutic Category: | -- |
| Clinical Trial Progress: | Clinical trial on-going (JPRN-UMIN000026635) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0554 | JPRN-UMIN000026635 | Not selected | Not Recruiting | No Results Available | 22/03/2017 | 27 September 2021 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A02469 | 34360923 | Int J Mol Sci | The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target. | Details |
| A06621 | 32805205 | Lancet Gastroenterol Hepatol | Lubiprostone in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled, phase 2a trial. | Details |
| A14029 | 29627620 | Contemp Clin Trials | Efficacy, safety, and tolerability of lubiprostone for the treatment of non-alcoholic fatty liver disease in adult patients with constipation: The LUBIPRONE, double-blind, randomised, placebo-controlled study design. | Details |
| A43017 | 32805206 | Lancet Gastroenterol Hepatol | Intestinal motility: a therapeutic target for NAFLD? | Details |
| A51428 | 35514019 | Dig Liver Dis | Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet-induced rat steatohepatitis. | Details |