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Namespace Prefixes

Prefix	IRI
n2	http://linked.opendata.cz/resource/drugbank/drug/
dcterms	http://purl.org/dc/terms/
n21	http://linked.opendata.cz/resource/drugbank/drug/DB08890/identifier/chebi/
n20	http://linked.opendata.cz/resource/AHFS/
foaf	http://xmlns.com/foaf/0.1/
n16	http://linked.opendata.cz/resource/drugbank/dosage/
n7	http://linked.opendata.cz/resource/drugbank/drug/DB08890/identifier/wikipedia/
n13	http://www.rxlist.com/
n19	http://bio2rdf.org/drugbank:
adms	http://www.w3.org/ns/adms#
n4	http://linked.opendata.cz/resource/drugbank/patent/
n10	http://linked.opendata.cz/resource/drugbank/drug/DB08890/identifier/kegg-drug/
n9	http://linked.opendata.cz/resource/drugbank/drug/DB08890/identifier/drugbank/
rdf	http://www.w3.org/1999/02/22-rdf-syntax-ns#
owl	http://www.w3.org/2002/07/owl#
n3	http://linked.opendata.cz/ontology/drugbank/
n12	http://www.drugs.com/cdi/
n8	http://linked.opendata.cz/resource/drugbank/property/
n6	http://linked.opendata.cz/resource/drugbank/drug/DB08890/identifier/national-drug-code-directory/
xsdh	http://www.w3.org/2001/XMLSchema#
n15	http://linked.opendata.cz/resource/atc/
n14	http://linked.opendata.cz/ontology/sukl/drug/

Statements

Subject Item: n2:DB08890
rdf:type: n3:Drug
n3:description: Linaclotide is an orally administered, peptide agonist of guanylate cyclase 2C for the treatment of irritable bowel syndrome. Chemically, it is a heterodetic cyclic peptide and consists of fourteen amino acids. The protein sequence is as follows: Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr. There are three disulfide bonds which are located between Cys1 and Cys6; between Cys2 and Cys10; and between Cys5 and Cys13. FDA approved on August 30, 2012.
n3:dosage: n16:271B5AFA-363D-11E5-9242-09173F13E4C5 n16:271B5AFB-363D-11E5-9242-09173F13E4C5 n16:271B5AFC-363D-11E5-9242-09173F13E4C5 n16:271B5AFD-363D-11E5-9242-09173F13E4C5
n3:generalReferences: # Busby RW, Kessler MM, Bartolini WP, Bryant AP, Hannig G, Higgins CS, Solinga RM, Tobin JV, Wakefield JD, Kurtz CB, Currie MG: Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. J Pharmacol Exp Ther. 2013 Jan;344(1):196-206. doi: 10.1124/jpet.112.199430. Epub 2012 Oct 22. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/23090647
n3:group: approved
n3:halfLife: Because linaclotide is not systemically absorbed, half life cannot be calculated.
n3:indication: Treatment of irritable bowel syndrome (IBS) with constipation and chronic idiopathic constipation.
owl:sameAs: n19:DB08890
dcterms:title: Linaclotide
adms:identifier: n6:0456-1202-30 n7:Linaclotide n9:DB08890 n10:D09355 n21:68551
n3:mechanismOfAction: Linaclotide is an agonist of guanylate cyclase-C (GC-C). Once linaclotide and its active metabolite binds to GC-C, it has local effect on the luminal surface of the intestinal epithelium. Activation of GC-C by linaclotide results in the intra- and extracellular increase of cyclic guanosine monophosphate concentrations (cGMP). This elevation of cGMP levels stimulates the secretion of chloride and bicarbonate into the intestinal lumen via activation of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. Ultimately, linaclotide helps patients with IBS (especially with constipation) as GI transit is accelerated and the release of intestinal fluid is increased. In animal models, a decrease in visceral pain after administration of linaclotide may be observed. A decrease in the activity of pain-sensing nerves occurs as a result of an increase in extracellular cGMP.
n3:patent: n4:8080526 n4:7304036 n4:7371727 n4:7704947 n4:7745409 n4:8110553
n3:routeOfElimination: Linaclotide is eliminated fecally (3 - 5% as active metabolites). However most of the dose undergoes proteolysis (processes include reduction of disulfide bonds) in the intestine before being excreted via feces.
n3:synonym: Linzess Cys cys glu tyr cys cys asn pro ala cys thr gly cys tyr (disulfide bridge: 1-6; 2-10; 5-13) L-Cysteinyl-L-cysteinyl-L-alpha-glutamyl-L-tyrosyl-L-cysteinyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-L-tyrosine cyclic (1->6),(2->10),(5->13)-tris(disulfide)
n3:toxicity: Most common adverse reactions (incidence of at least 2%) reported in IBS-C or CIC patients are diarrhea, abdominal pain, flatulence and abdominal distension.
n3:volumeOfDistribution: Given that linaclotide plasma concentrations following therapeutic oral doses are not measurable, linaclotide is expected to be minimally distributed to tissues.
n14:hasAHFSCode: n20:56-92
n3:foodInteraction: Even when taken with food, linaclotide does not reach detectable levels in the plasma. However, when taken with a high fat meal, one may observe looser stools and a higher stool frequency.
n3:salt
foaf:page: n12:linaclotide.html n13:linzess-drug.htm
n3:IUPAC-Name: n8:271B5B02-363D-11E5-9242-09173F13E4C5
n3:InChI: n8:271B5B08-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula: n8:271B5B07-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight: n8:271B5B04-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight: n8:271B5B05-363D-11E5-9242-09173F13E4C5
n3:SMILES: n8:271B5B06-363D-11E5-9242-09173F13E4C5
n3:Water-Solubility: n8:271B5B18-363D-11E5-9242-09173F13E4C5 n8:271B5B00-363D-11E5-9242-09173F13E4C5
n3:logP: n8:271B5B01-363D-11E5-9242-09173F13E4C5 n8:271B5AFE-363D-11E5-9242-09173F13E4C5
n3:logS: n8:271B5AFF-363D-11E5-9242-09173F13E4C5
n14:hasATCCode: n15:A06AX04
n3:H-Bond-Acceptor-Count: n8:271B5B0E-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count: n8:271B5B0F-363D-11E5-9242-09173F13E4C5
n3:InChIKey: n8:271B5B09-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-: n8:271B5B0A-363D-11E5-9242-09173F13E4C5
n3:Polarizability: n8:271B5B0C-363D-11E5-9242-09173F13E4C5
n3:Refractivity: n8:271B5B0B-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count: n8:271B5B0D-363D-11E5-9242-09173F13E4C5
n3:absorption: When taken orally, linaclotide is not absorbed into the systemic. No detectable levels of linaclotide or its active metabolite were noted after doses of 125 mcg or 290 mcg were administered.
n3:affectedOrganism: Humans and other mammals
n3:casRegistryNumber: 851199-59-2
n3:Bioavailability: n8:271B5B14-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter: n8:271B5B16-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule: n8:271B5B17-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings: n8:271B5B13-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge: n8:271B5B12-363D-11E5-9242-09173F13E4C5
n3:Rule-of-Five: n8:271B5B15-363D-11E5-9242-09173F13E4C5
n3:Traditional-IUPAC-Name: n8:271B5B03-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-acidic-: n8:271B5B10-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-basic-: n8:271B5B11-363D-11E5-9242-09173F13E4C5