Plecanatide is a minimally absorbed agonist of guanylate cyclase C receptors in the intestine and is used for treatment of chronic constipation and irritable bowel syndrome. Plecanatide has not been linked to serum enzyme elevations during treatment or to episodes of clinically apparent liver injury.
CAT No: 10-101-170
CAS No:467426-54-6
Synonyms/Alias:PLECANATIDE;Trulance;Guanilib;467426-54-6;UNII-7IK8Z952OK;plecanatida;Plecanatide [USAN:INN];7IK8Z952OK;HSDB 8405;SP-304 (SYNERGY);DTXSID60196933;(3-Glutamic acid(D>E))human uroguanylin (UGN);467426-54-6 (free base);L-Leucine, L-asparaginyl-L-alpha-aspartyl-L-alpha-glutamyl-L-cysteinyl-L-alpha-glutamyl-L-leucyl-L- cysteinyl-L-valyl-L-asparaginyl-L-valyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-, cyclic (4->12),(7->15)-bis(disulfide);(3-Glutamic acid(D>E))human uroguanylin;[3-glutamic acid(D>E)]human uroguanylin;plecanatidum;Plecanatide (Standard);TrulanceImmediate release;GTPL9069;CHEMBL2103867;A06AX07;DTXCID00119424;GLXC-26182;EX-A4131;AT41877;DB13170;HY-108741R;DA-56928;ASN-ASP-GLU-CYS-GLU-LEU-CYS-VAL-ASN-VAL-ALA-CYS-THR-GLY-CYS-LEU CYCLIC (4->12),(7->15)-BIS(DISULFIDE);L-asparaginyl-L-alpha-aspartyl-L-alpha-glutamyl-L-cysteinyl-L-alpha-Glutamyl-L-leucyl-L-cysteinyl-L-valyl-L-asparaginyl-L-valyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-L-leucine cyclic (4-->12),(7-->15)-bis(disulfide);L-asparaginyl-L-alpha-aspartyl-L-alpha-glutamyl-L-cysteinyl-L-alpha-Glutamyl-L-leucyl-L-cysteinyl-L-valyl-L-asparaginyl-L-valyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-L-leucine cyclic (4adagger?2),(7adagger?5)-bis(disulfide);L-LEUCINE, L-ASPARAGINYL-L-alpha-ASPARTYL-L-alpha-GLUTAMYL-L-CYSTEINYL-L-alpha-GLUTAMYL-L-LEUCYL-L-CYSTEINYL-L-VALYL-L-ASPARAGINYL-L-VALYL-L-ALANYL-L-CYSTEINYL-L-THREONYLGLYCYL-L-CYSTEINYL-, CYCLIC (4-12),(7-15)-BIS(DISULFIDE);
Plecanatide is a synthetic peptide analog structurally related to the endogenous human peptide uroguanylin, designed to mimic its natural physiological effects in the gastrointestinal tract. Featuring a sequence optimized for stability and receptor selectivity, Plecanatide is characterized by its ability to activate guanylate cyclase-C (GC-C) receptors located on the luminal surface of intestinal epithelial cells. This targeted agonism leads to increased production of intracellular cyclic guanosine monophosphate (cGMP), setting off a cascade of downstream effects that modulate ion and fluid transport within the gut. The compound's unique molecular design ensures robust bioactivity and resistance to enzymatic degradation, making it a valuable tool in research settings focused on gastrointestinal physiology and signaling pathways.
Gastrointestinal Motility Research: In studies investigating the mechanisms underlying intestinal transit and motility, Plecanatide serves as a precise tool for modulating GC-C receptor activity. By promoting cGMP-mediated chloride and bicarbonate secretion into the intestinal lumen, it facilitates increased fluid movement, which in turn helps to model and analyze the physiological processes governing bowel movement. Researchers utilize this peptide to dissect the intricate signaling networks that regulate peristalsis and to identify novel targets for addressing motility disorders. Its application in ex vivo and in vitro gastrointestinal tissue models allows for controlled experimentation on epithelial transport and secretory dynamics without the confounding variables present in whole-animal systems.
Ion Transport and Epithelial Barrier Function: The compound's ability to induce cGMP production has made it indispensable for probing the molecular mechanisms of ion transport across epithelial barriers. Through activation of the CFTR chloride channel and modulation of tight junction proteins, Plecanatide enables detailed studies on how electrolyte and water balance is maintained in the gut. Researchers deploy it in cell culture models to assess changes in transepithelial electrical resistance and paracellular permeability, advancing the understanding of barrier integrity in health and disease. This application is particularly relevant for exploring the pathogenesis of gastrointestinal disorders characterized by disrupted barrier function, such as inflammatory bowel diseases.
Signal Transduction Pathway Elucidation: Scientists employ Plecanatide in experimental systems to unravel the complexity of GC-C mediated signaling cascades. By selectively triggering this receptor, it allows for the isolation and characterization of downstream effectors, including protein kinases, phosphodiesterases, and transcription factors influenced by cGMP. This approach aids in mapping out the broader physiological roles of guanylate cyclase signaling beyond fluid secretion, such as its involvement in cellular proliferation, apoptosis, and immune modulation within the gut mucosa. The peptide's specificity and potency make it an ideal candidate for dissecting the temporal and spatial aspects of these pathways in both normal and pathological contexts.
Pharmacological Screening and Drug Discovery: As a well-characterized GC-C agonist, Plecanatide is frequently incorporated into high-throughput screening assays designed to identify novel modulators of intestinal function. Its use as a reference compound enables comparative evaluation of new chemical entities targeting the same receptor or related signaling mechanisms. Additionally, it provides a benchmark for assessing the efficacy and selectivity of potential therapeutic candidates in preclinical research. By facilitating the development of innovative agents aimed at restoring gut homeostasis, Plecanatide contributes to the advancement of gastrointestinal pharmacology.
Comparative Physiology and Translational Research: In comparative studies exploring species-specific differences in intestinal physiology, the peptide is utilized to assess the conservation and divergence of GC-C signaling pathways across various animal models. This research direction supports the translation of basic scientific findings into broader biological contexts and informs the selection of appropriate models for future investigations. By enabling cross-species comparisons of receptor pharmacodynamics and downstream effects, Plecanatide enhances the understanding of evolutionary adaptations in gut function and informs strategies for optimizing experimental design in translational research.
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