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| 1 | Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases. | Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 5 |
| 2 | Lewis acid metal ion-exchanged MAPO-5 molecular sieves for solvent free synthesis of coumarin derivative显示文摘 | GOPALAKRISHNAN S VISWANATHAN K R PRIYA S V MABEL J H PALANICHAMY M MURUGESAN V | 2008 | Catalysis Communications2008，10，10： | 1 |
| 3 | Advances in energy harvesting using tow profile piezoelectric transducers 显示文摘 | PRIYA S | 2007 | J Electroceram2007，19，16： | 1 |
| 4 | Effect of nanoseale CeO2 on P(VDF-HFP)-based nanocomposite porous polymer electrolytes for Li-ion batteries显示文摘 | G Vijayakumar S N Karthick A R Sathiya Priya | 2008 | Journal State Electrochem2008，12，： | 1 |
| 5 | Induction of apoptosis and cell cycle arrest by Bis (2 ethylhexyl) phthalate produced by marine Bacilluspumilus MB40 显示文摘 | Moushumi Priya A Jayachandran S | 2012 | ChemBiolInteract2012，195，2： | 1 |
| 6 | Piezoelectric and magnetoelectric thick films for fabricating power sources in wireless sensor nodes显示文摘 | PRIYA S RYU J PARK C S el al | 2009 | Sensors2009，9，： | 1 |
| 7 | Simuhaneous bioconversion of cel- lulose and hemicellulose to ethanol显示文摘 | Priya Chandrakant Bisaria V S | 1998 | Critical Reviews in Biotechnology1998，18，4： | 1 |
| 8 | Piezoelectric MEMS for energy harvesting 显示文摘 | KIM S G PRIYA S KANNO I | 2012 | Mrs Bull2012，37，10： | 1 |
| 9 | Folasade ekulona and barbara smith, an improved genetic system for bioengi- neering buoyant gas vesicle nanoparticles from haloar- chaea显示文摘 | Dassarma S Karan R Priya D el al | 2013 | BMC Biotechnol2013，196，13： | 1 |
| 10 | Advances in energy harvesting using low profile piezoelectric transducers 显示文摘 | Priya S | 2007 | Journal of Electroceramics2007，19，1： | 1 |
| 11 | Association of interleukin-10 gene promoter poIy- morphism in allergic patients显示文摘 | GADDAM S L PRIYA V H S BABU B M V S | 2012 | Genet Test Mol Bi- omarkers2012，16，： | 1 |
| 12 | Piezoelectric En- ergy Harvesting Under High Pre-stressed Cyclic Vibra tions显示文摘 | Kim H W Priya S Uchino K | 2005 | Journal of Electroceramics2005，15，1： | 1 |
| 13 | Realization of high-energy density polycrystalline piezoelectric ceramics 显示文摘 | ISLAM R A PRIYA S | 2006 | Appl Phys Lett2006，88，03： | 1 |
| 14 | Autoimmune thyroid disease in patients with vitiligo: prevalence study in India显示文摘 | Kumar KV Priya S Sharrna R | 2012 | Endocr Pract2012，18，2： | 1 |
| 15 | Synthesis of pharmaceutically important condensed heterocyclic 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivatives as antimicrobials显示文摘 | Swamy S N Priya B S Prabhuswamy B | 2006 | Eur J Med Chem2006，41，4： | 1 |
| 16 | Characterization of mechanical and electrical properties of epoxy-glass microballoon syntactic composites显示文摘 | GUPTA N PRIYA S ISLAM R | 2006 | Ferroelectrics2006，345，1： | 1 |
| 17 | Effect of hydrophobic and hydrophilic properties of solid acid catalysts on the esterification of mateic anhydride with ethanol显示文摘 | Bhagiyalakshmi M Priya S V Mabel J H | 2008 | Catalysis Communications2008，9，10： | 1 |
| 18 | Protein Kinase C is up regulated in osteoarthntic cartilage and is required for activalion of NF - κB by lumot necrosis factor and interleukin - 1 in articular chondrocytes 显示文摘 | Edward R LVER Priya S | 2006 | J Biol Chem2006，281，24： | 1 |
| 19 | A thermodynamic study of liquid Cu-Cr alloys and metastable liquid immiscibility显示文摘 | Jacob K T Priya S Waseda Y | 2000 | Z Metal2000，，91： | 1 |
| 20 | Effect of Simultaneous Exposure to Lead and Cadmium on Gonadotropin Binding and Steroidogenesis on Granulosa Cells:An in Vitro Study显示文摘 | Priya P N Pillai A Gupta S | 2004 | Indian J Exp Bio12004，42，2： | 1 |
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