{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:52:21Z","timestamp":1792129941782,"version":"4.4.0"},"reference-count":95,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T00:00:00Z","timestamp":1430352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Iuventus Plus program of the Polish Ministry of Science and Higher Education","award":["0107\/IP1\/2013\/72 to JF"],"award-info":[{"award-number":["0107\/IP1\/2013\/72 to JF"]}]},{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"crossref","award":["503\/1-156-04\/503-01 to JF and 502-03\/1-156-02\/502-14-141 to MZ"],"award-info":[{"award-number":["503\/1-156-04\/503-01 to JF and 502-03\/1-156-02\/502-14-141 to MZ"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"crossref","award":["UMO-2013\/11\/B\/NZ7\/01301 and #507\/1-156-04\/507-10-078 to MZ, #UMO-2013\/11\/B\/NZ7\/01301 to JF"],"award-info":[{"award-number":["UMO-2013\/11\/B\/NZ7\/01301 and #507\/1-156-04\/507-10-078 to MZ, #UMO-2013\/11\/B\/NZ7\/01301 to JF"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Functional gastrointestinal disorders (<jats:styled-content style=\"fixed-case\">FGID<\/jats:styled-content>) and inflammatory bowel diseases (<jats:styled-content style=\"fixed-case\">IBD<\/jats:styled-content>) are the most frequent pathologic conditions affecting the gastrointestinal (<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>) tract and both significantly reduce patients\u2019 quality of life. Recent studies suggest that guanylyl cyclase C (<jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010C) expressed in the<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>tract constitutes a novel pharmacological target in the treatment of<jats:styled-content style=\"fixed-case\">FGID<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">IBD<\/jats:styled-content>. Endogenous<jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010C agonists \u2013 guanylin peptides: guanylin and uroguanylin, by the regulation of water and electrolyte transport, are involved in the maintenance of homeostasis in the intestines and integrity of the intestinal mucosa. Linaclotide, a synthetic agonist of<jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010C was approved by Food and Drug Administration and European Medicines Agency as a therapeutic in constipation\u2010predominant irritable bowel syndrome (<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010C) and chronic idiopathic constipation (CIC). Lately, several preclinical and clinical trials focused on assessment of therapeutic properties of synthetic agonists of uroguanylin, plecanatide, and<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>\u2010333. Plecanatide is currently tested as a potential therapeutic in diseases related to constipation and<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>\u2010333 is a promising drug in ulcerative colitis treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Here, we discuss the most recent findings and future trends on the development of<jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\u2010C agonists and their use in clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12574","type":"journal-article","created":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T02:55:52Z","timestamp":1430448952000},"page":"1057-1068","source":"Crossref","is-referenced-by-count":15,"title":["Emerging treatments in Neurogastroenterology: Perspectives of guanylyl cyclase C agonists use in functional gastrointestinal disorders and inflammatory bowel diseases"],"prefix":"10.1111","volume":"27","author":[{"given":"A.","family":"Jarmu\u017c","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Zieli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Storr","sequence":"additional","affiliation":[{"name":"Walter Brendel Center of Experimental Medicine Ludwig Maximilians University Munich Munich Germany"},{"name":"Center of Endoscopy Starnberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Fichna","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2004.04114.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.061"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MIB.0000436277.13917.c4"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2014.06.004"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2012.10.005"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins2082028"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.261"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S32252"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e328341ead5"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2014.00031"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-013-2684-z"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","unstructured":"ShailubhaiK FossJ ZhangG ArjunanKP FengR ComiskeyS JacobS PlevySE.SP\u2010333 a Guanylate Cyclase\u2010C Agonist Ameliorates DSS\u2010Colitis in Mice Via a Novel Cyclic GMP\u2010Mediated Mechanism (P\u2010198). Poster presentation at: Advances in Inflammatory Bowel Diseases Crohn's & Colitis Foundation's Clinical & Research Conference 2012.","DOI":"10.1097\/00054725-201212001-00231"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0031-6997(24)01457-1","article-title":"Guanylyl cyclases and signaling by cyclic GMP","volume":"52","author":"Lucas KA","year":"2000","journal-title":"Pharmacol Rev"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1014231722696"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00488.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9629(96)00307-6"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335767"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb13024.x"},{"issue":"4","key":"e_1_2_11_20_1","first-page":"G633","article-title":"Regulation of intestinal Cl\u2010 and HCO3\u2010secretion by uroguanylin","volume":"274","author":"Joo NS","year":"1998","journal-title":"Am J Physiol"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06355.x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(96)70018-5"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v112.pm9024297"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.4.1466"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70419-7"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.5402\/2013\/813648"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(97)01078-1"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.6.2046"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.19.9089"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.22.10464"},{"issue":"1","key":"e_1_2_11_31_1","first-page":"G93","article-title":"Signal transduction pathways via guanylin and uroguanylin in stomach and intestine","volume":"273","author":"London RM","year":"1997","journal-title":"Am J Physiol"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)81387-2"},{"issue":"2","key":"e_1_2_11_33_1","first-page":"F342","article-title":"Characterization of human uroguanylin: a member of the guanylin peptide family","volume":"266","author":"Kita T","year":"1994","journal-title":"Am J Physiol"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(96)01235-5"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.344"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70197-5"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.8.2935"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.139.12.5247"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70198-7"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.424"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2705"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.142.7.3087"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(96)70037-9"},{"issue":"4","key":"e_1_2_11_44_1","first-page":"G708","article-title":"Opossum colonic mucosa contains uroguanylin and guanylin peptides","volume":"270","author":"Hamra FK","year":"1996","journal-title":"Am J Physiol"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050054"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-010-0131-2"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.34.794"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2917"},{"key":"e_1_2_11_49_1","first-page":"101","article-title":"Guanylin mRNA expression in human intestine and colorectal adenocarcinoma","volume":"78","author":"Cohen MB","year":"1998","journal-title":"Lab Invest"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141124698"},{"key":"e_1_2_11_51_1","first-page":"5151","article-title":"Uroguanylin treatment suppresses polyp formation in the Apc(Min\/+) mouse and induces apoptosis in human colon adenocarcinoma cells via cyclic GMP","volume":"60","author":"Shailubhai K","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-131-11-199912070-00002"},{"key":"e_1_2_11_53_1","first-page":"739","article-title":"Ectopic expression of guanylyl cyclase C in adenocarcinomas of the esophagus and stomach","volume":"11","author":"Park J","year":"2002","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i37.5151"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2004.01938.x"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.02.029"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1207068"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.12.047"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.2741\/E583"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00542.2011"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2006.00771.x"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000034"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2008.07.003"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00127"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.227132"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/548024"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.199430"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.09.019"},{"key":"e_1_2_11_69_1","first-page":"154","article-title":"Linaclotide (linzess) for irritable bowel syndrome with constipation and for chronic idiopathic constipation","volume":"38","author":"Thomas RH","year":"2013","journal-title":"P T"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2009.01385.x"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.08.017"},{"key":"e_1_2_11_72_1","doi-asserted-by":"crossref","unstructured":"MinerPBJr DeLucaR De La PortillaM PadillaE KoltunW WiltzO ShailubhaiK JacobGSet\u00a0al.Plecanatide a Novel Uroguanylin Analog: a 12\u2010week randomized double\u2010blind placebo\u2010controlled dose\u2010ranging trial to evaluate efficacy and safety in patients with irritable bowel syndrome with constipation (IBS\u2010C). Program No. 14. ACG 2014 Annual Scientific Meeting Abstracts. Philadelphia PA: American College of Gastroenterology;2014. Available from:http:\/\/www.eventscribe.com\/2014\/acg\/PostersTitles.asp?sort=num&dir=&h=Browse%20by%20Number","DOI":"10.14309\/00000434-201410002-01831"},{"key":"e_1_2_11_73_1","unstructured":"KrauseRA.Open\u2010label Extension (OLE) Study of Plecanatide for Chronic Idiopathic Constipation (CIC). ClinicalTrials.gov Identifier: NCT01919697.2013."},{"key":"e_1_2_11_74_1","unstructured":"WinkleP.Single Ascending Dose Study to Evaluate the Safety Tolerability and Pharmacokinetics (PK) of SP\u2010333 Tablets in Healthy Adult Subjects. ClinicalTrials.gov Identifier: NCT01705938.2012."},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.255"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.254"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1010863"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2014.04.005"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2012.11.012"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.10.001"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-006-9054-5"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00603.x"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8553(01)00002-4"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-2980.2010.00449.x"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X10361304"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804647"},{"key":"e_1_2_11_87_1","unstructured":"SJ Comiskey JA Foss GS Jacob K Shailubhai 2012"},{"key":"e_1_2_11_88_1","unstructured":"PhilipBM.The Plecanatide Irritable Bowel Syndrome With Constipation Study (IBS\u2010C) (CIBS). ClinicalTrials.gov Identifier: NCT01722318.2012."},{"key":"e_1_2_11_89_1","article-title":"Plecanatide, a novel guanylate cyclase C receptor agonist, is efficacious and safe in patients with chronic idiopathic constipation: results from a 951 patient, 12\u00a0week, multi\u2010center trial","author":"Philip BM","year":"2013","journal-title":"Digestive Disease Week"},{"key":"e_1_2_11_90_1","article-title":"Guanylate cyclase C agonists, a new class of drug candidates for treatment of inflammatory bowel disease","author":"Shailubhai K","year":"2011","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_11_91_1","article-title":"Guanylate cyclase C agonists as a new class of drug candidates to delay progression of colitis to colonic tumors in ApcMin\/+ mice","author":"Shailubhai K","year":"2011","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2004.021840"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03506.x"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01099.x"},{"key":"e_1_2_11_95_1","article-title":"SP\u2010333, a proteolysis\u2010resistant agonist of guanylate cyclase\u2010C, inhibits activation of NF\u2010kB and supress production of inflammatory cytokines to ameliorate DSS\u2010induced colitis in mice","author":"Graham Z","year":"2012","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_11_96_1","unstructured":"RenataT.Dose\u2010ranging Study to Assess Safety and Efficacy of SP\u2010333 for the Treatment of Opioid\u2010induced Constipation (OIC). ClinicalTrials.gov Identifier: NCT01983306.2013."}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnmo.12574","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.12574","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T19:16:38Z","timestamp":1748373398000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.12574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,30]]},"references-count":95,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1111\/nmo.12574"],"URL":"https:\/\/doi.org\/10.1111\/nmo.12574","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,30]]}}}