LUBIPROSTONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H32F2O5
Molecular Weight	390.4619
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC(=O)[C@H](CCCCCCC(O)=O)[C@@]1([H])CC[C@@](O)(O2)C(F)(F)CCCC

InChI

InChIKey=WGFOBBZOWHGYQH-MXHNKVEKSA-N

InChI=1S/C20H32F2O5/c1-2-3-11-19(21,22)20(26)12-10-15-14(16(23)13-17(15)27-20)8-6-4-5-7-9-18(24)25/h14-15,17,26H,2-13H2,1H3,(H,24,25)/t14-,15-,17-,20-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C20H32F2O5
Molecular Weight	390.4619
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB01046
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/021908Orig1s008.pdf

Lubiprostone is a medication used in the management of idiopathic chronic constipation. It is a bicyclic fatty acid (prostaglandin E1 derivative) which acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements (SBM). 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. Lubiprostone is marketed under the trade name Amitiza among others.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Chloride channel protein 2 1 Target ID: CHEMBL1628478 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/021908Orig1s008.pdf \| http://www.drugbank.ca/drugs/DB01046	Activator 1410
Prostanoid EP4 receptor 10 Target ID: CHEMBL1836 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18332851 \| https://www.ncbi.nlm.nih.gov/pubmed/22960173 \| https://www.ncbi.nlm.nih.gov/pubmed/23001408	Agonist 2662

Conditions

Condition	Modality	Targets	Highest Phase	Product
Constipation 112 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/021908Orig1s008.pdf	Primary		Approved 8360	Amitiza Approved Use Amitiza is a chloride channel activator indicated for: • Treatment of chronic idiopathic constipation in adults • Treatment of irritable bowel syndrome with constipation in women ≥ 18 years old Launch Date 1.13857921E12

C_max

Value	Dose	Co-administered	Analyte	Population
41.5 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf	24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered:		15-HYDROXY LUBIPROSTONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
37.5 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf	24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered:		15-HYDROXY LUBIPROSTONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
57.1 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf	24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered:		15-HYDROXY LUBIPROSTONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
39.6 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf	24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered:		15-HYDROXY LUBIPROSTONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.15 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf	24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered:		15-HYDROXY LUBIPROSTONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
6% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf	24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered:		15-HYDROXY LUBIPROSTONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
24 ug 2 times / day multiple, oral Recommended Dose: 24 ug, 2 times / day Route: oral Route: multiple Dose: 24 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf Page: p.1, 4	unhealthy n = 1113 Health Status: unhealthy Condition: Chronic idiopathic constipation Population Size: 1113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf Page: p.1, 4	Disc. AE: Nausea, Dyspnea... AEs leading to discontinuation/dose reduction: Nausea (9%) Dyspnea (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf Page: p.1, 4
144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf Page: p.8	healthy n = 51 Health Status: healthy Population Size: 51 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf Page: p.8	Other AEs: Nausea, Diarrhea... Other AEs: Nausea (45%) Diarrhea (35%) Vomiting (27%) Dizziness (14%) Headache (12%) Abdominal pain (8%) Flash hot (8%) Retching (8%) Dyspnea (4%) Pallor (4%) Stomach discomfort (4%) Anorexia (2%) Asthenia (2%) Chest discomfort (2%) Dry mouth (2%) Hyperhidrosis (2%) Syncope (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf Page: p.8

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579 inducer 768	inhibitor 1752 inducer 383	inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2A6 704 CYP2B6 799 CYP2C19 1463 CYP2E1 876 CYP 110	CYP 266	CYP1A2 689 CYP2B6 538 CYP 76

Drug as perpetrator

Target	Modality	Activity
CYP2A6 736	supressor 155 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 6, 15	likely
CYP 146	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 6, 14	no
CYP 146	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 6, 14	no
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP2C9 1803	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 15.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 266	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 6, 14, 19	no

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific, Inc. (AKSCI)	N917	http://www.aksci.com/item_detail.php?cat=N917
AK Scientific, Inc. (AKSCI)	X6870	http://www.aksci.com/item_detail.php?cat=X6870
AK Scientific, Inc. (AKSCI)	Z6115	http://www.aksci.com/item_detail.php?cat=Z6115
AbMole Bioscience	M3459	http://www.abmole.com/products/lubiprostone.html
Alfa Chemistry	AP136790766	https://reagents.alfa-chemistry.com/product/lubiprostone-cas-136790-76-6-4303.html
Alichem	119001436	http://www.alichem.com/en/products/333963-40-9.html
Allbio Pharm Co., Ltd	AF09449	http://www.allbiopharm.com/product/n/AF09449
Ambinter	Amb17772254	http://www.ambinter.com/reference/17772254
Angene	AGN-PC-0R8X2U	http://www.angenechemical.com/productshow/AGN-PC-0R8X2U.html
ApexBio Technology	B2108	http://www.apexbt.com/lubiprostone.html
AvaChem Scientific	2629	http://www.avachem.com/productSearch.asp?2629
BLD Pharm	BD449029	http://www.bldpharm.com/products/333963-40-9.html
BioSynth	J-006909	https://www.biosynth.com/en/products/all-products/products/J-006909.html
Boerchem	BC677681	http://www.boerchem.com/?product_39566.html
ChemFish Tokyo co.,ltd	157920	http://www.chemfish.co.jp/index.php?id=2925&project=product
ChemMol	30108352	http://www.chemmol.com/chemmol/30108352.html
ChemMol	44009988	http://www.chemmol.com/chemmol/44009988.html
ChemMol	49401148	http://www.chemmol.com/chemmol/49401148.html
Chemspace	CSSB00020619493	https://chem-space.com/CSSB00020619493
DC Chemicals	DC8287	http://www.dcchemicals.com/product_show-Lubiprostone.html
Excenen	EX-A1771	http://www.excenen.com/searchresultlist.php?id=333963-40-9
Fluoropharm	YF10093	http://www.fluoropharm.com/product/YF10093.html
Hairui	HR124861	http://www.hairuichem.com/en/product/136790-76-6.html
Hairui	HR34159	http://www.hairuichem.com/en/product/333963-40-9.html
MuseChem	I007731	https://www.musechem.com/product/I007731.html
OChem	26475	http://www.ocheminc.com/index.php?act=psearch&pid=963L409
Renno Tech	RP17713	http://www.rennotech.com/product_show.asp?id=23591
Renno Tech	RL03218	http://www.rennotech.com/product_show.asp?id=3467
Smolecule	S533727	http://www.smolecule.com/products/s533727
THE BioTek	bt-274371	https://www.thebiotek.com/product/inhibitors/bt-274371
THE BioTek	bt-315004	https://www.thebiotek.com/product/others/bt-315004
THE BioTek	bt-461346	https://www.thebiotek.com/product/others/bt-461346
Tenova Pharmaceuticals Inc	T31084	https://www.tenovapharma.com/Lubiprostone
Yuhao Chemical	LX2755	http://www.chemyuhao.com/136790-76-6.html
abcr GmbH	AB456001	http://www.abcr.com/shop/en/AB456001
eNovation Chemicals	D371587	http://www.enovationchem.com/productDetails.asp?productID=D371587
eNovation Chemicals	D630727	https://www.enovationchem.com/ProductDetails.asp?ProductID=D630727
eNovation Chemicals	Y0974121	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0974121
eNovation Chemicals	Y1082345	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y1082345
iChemical	EBD2197415	http://www.ichemical.com/products/136790-76-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
iChemical	EBD3052237	http://www.ichemical.com/products/333963-40-9.html

PubMed

Title	Date	PubMed
SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents.	2004 Nov	15213059
Lubiprostone: RU 0211, SPI 0211.	2005	15991886
Gateways to clinical trials.	2005 May	16082427
Lubiprostone.	2005 May	15883925
Treating chronic constipation : How should we interpret the recommendations?	2006	17163288
Lubiprostone: viewpoints.	2006	16706563
Lubiprostone.	2006	16706562
Defecation disorders: neuromuscular aspects and treatment.	2006 Aug	16888870
Lubiprostone: chloride channel activator for chronic constipation.	2006 Dec	17296458
Gateways to clinical trials.	2006 Jan-Feb	16541195
Current gut-directed therapies for irritable bowel syndrome.	2006 Jul	16836950
Chronic constipation: let symptom type and severity direct treatment.	2006 Jul	16822445
Lubiprostone (amitiza) for chronic constipation.	2006 Jun 5	16770297
Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers.	2006 May	16603730
New drugs: lubiprostone, ranolazine, and anidulafungin.	2006 May-Jun	16739767
Gateways to clinical trials.	2006 Sep	17003851
Lubiprostone: a chloride channel activator.	2007 Apr	17413599
Chloride transporting capability of Calu-3 epithelia following persistent knockdown of the cystic fibrosis transmembrane conductance regulator, CFTR.	2007 Apr	17339840
Lubiprostone: a new drug for the treatment of chronic idiopathic constipation.	2007 Fall	18192957
New drugs 07, part I.	2007 Feb	17273084
Drug approvals.	2007 Feb	17264794
Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone.	2007 Feb	17053162
Activation of type-2 chloride channels: a novel therapeutic target for the treatment of chronic constipation.	2007 Jan	17263187
Constipation in long-term care.	2007 May	17498603
Managing the chronically constipated adult: emerging approaches to diagnosis and treatment.	2007 Sep	17936941
Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation.	2008 Apr	18248656
A synthetic prostone activates apical chloride channels in A6 epithelial cells.	2008 Aug	18511742
Lubiprostone for constipation and irritable bowel syndrome with constipation.	2008 Dec	19090733
Lubiprostone: easing the strain of constipation?	2008 Jan	18166366
Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation.	2008 Jan	17916109
Conquering IBS in women: the clinician's pursuit of optimum management strategies.	2008 Jul	18845915
Development of drugs for gastrointestinal motor disorders: translating science to clinical need.	2008 Mar	18257767
[Functional and motor gastrointestinal disorders].	2008 Oct	19434861
Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine.	2008 Oct 21	18932279
Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model.	2008 Oct 3	18833323
Management of constipation in the elderly: emerging therapeutic strategies.	2008 Sep 7	18777602
Treatment of dysautonomia associated with Parkinson's disease.	2009 Dec	20082997
Lubiprostone: chronic constipation and irritable bowel syndrome with constipation.	2009 Jan	19236188
To the editor. CLC chloride channels and transporters: from genes to protein structure, pathology and physiology.	2009 Jun	19514889
[New drugs for the treatment of constipation].	2010 Jul	20676949

Patents

Sample Use Guides

In Vivo Use Guide

Chronic idiopathic constipation • 24 mcg taken twice daily orally with food and water Irritable bowel syndrome with constipation • 8 mcg taken twice daily orally with food and water

Route of Administration: Oral

In Vitro Use Guide

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

Substance Class	Chemical Created by `admin` on `Thu Jul 06 22:12:54 UTC 2023` Edited by `admin` on `Thu Jul 06 22:12:54 UTC 2023`
Record UNII	7662KG2R6K
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LUBIPROSTONE

Official Name

English

AMITIZA

Brand Name

English

LUBIPROSTONE [JAN]

Common Name

English

RU-0211

Code

English

lubiprostone [INN]

Common Name

English

Lubiprostone [WHO-DD]

Common Name

English

7-[(2R,4aR,5R,7aR)-2-(1,1-Difluoropentyl)-2-hydroxy-6-oxooctahydrocyclopenta[b]pyran-5-yl]heptanoic acid

Systematic Name

English

LUBIPROSTONE [USAN]

Common Name

English

(-)-7-((2R,4AR,5R,7AR)-2-(1,1-DIFLUOROPENTYL)-2-HYDROXY-6-OXOOCTAHYDROCYCLOPENTA(B)PYRAN-5-YL)HEPTANOIC ACID

Common Name

English

LUBIPROSTONE [VANDF]

Common Name

English

LUBIPROSTONE [ORANGE BOOK]

Common Name

English

LUBIPROSTONE [MI]

Common Name

English

PROSTAN-1-OIC ACID, 16,16-DIFLUORO-11-HYDROXY-9,15-DIOXO-, (11.ALPHA.)-

Common Name

English

LUBIPROSTONE [MART.]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175456