Emerging treatments in Neurogastroenterology: Perspectives of guanylyl cyclase C agonists use in functional gastrointestinal disorders and inflammatory bowel diseases.
BACKGROUND
Functional gastrointestinal disorders (FGID) and inflammatory bowel diseases (IBD) are the most frequent pathologic conditions affecting the gastrointestinal (GI) tract and both significantly reduce patients' quality of life. Recent studies suggest that guanylyl cyclase C (GC-C) expressed in the GI tract constitutes a novel pharmacological target in the treatment of FGID and IBD. Endogenous GC-C agonists - 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 GC-C was approved by Food and Drug Administration and European Medicines Agency as a therapeutic in constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC). Lately, several preclinical and clinical trials focused on assessment of therapeutic properties of synthetic agonists of uroguanylin, plecanatide, and SP-333. Plecanatide is currently tested as a potential therapeutic in diseases related to constipation and SP-333 is a promising drug in ulcerative colitis treatment.


OBJECTIVE
Here, we discuss the most recent findings and future trends on the development of GC-C agonists and their use in clinical trials.
Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
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Jarmuż
Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
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Zielińska
Walter Brendel Center of Experimental Medicine, Ludwig Maximilians University Munich, Munich, Germany.|Center of Endoscopy, Starnberg, Germany.
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Storr
Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
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Fichna
D002986:Clinical Trials as Topic; D003248:Constipation / Q000188:drug therapy; D005260:Female; D005762:Gastroenterology / Q000639:trends*; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D005768:Gastrointestinal Hormones / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D045265:Natriuretic Peptides / Q000378:metabolism / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled / Q000819:agonists* / Q000378:metabolism; D018000:Receptors, Peptide / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction
D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; D018000:Receptors, Peptide; C072685:guanylin; C084362:uroguanylin; C584575:plecanatide; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; C523483:linaclotide
SP-333; guanylin; guanylyl cyclase C agonists; linaclotide; plecanatide; uroguanylin