| Identification | Back Directory | [Name]
Plecanatide | [CAS]
467426-54-6 | [Synonyms]
Trulance
Pukanatide
ATCH(1-39)
Prikanatide
Plecanatide
Plecanatide impurity
Plecanatide USP/EP/BP
Plecanatide Impurtiy
ASN-ASP-GLU-CYS-GLU-LEU-CYS-VAL-ASN-VAL-ALA-CYS-THR-GLY-CYS-LEU(DISULFIDE BOND CYS1&CYS3,CYS2&CYS4)
L-Leucine, L-asparaginyl-L-α-aspartyl-L-α-glutamyl-L-cysteinyl-L-α-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)
(4S)-4-[(2S)-2-[(2S)-2-amino-3-carbamoylpropanamido]-3-carboxypropanamido]-4-{[(1R,4S,7S,10S,13S,16R,19S,22S,25R,32S,38R)-10-(carbamoylmethyl)-38-{[(1S)-1-carboxy-3-methylbutyl]carbamoyl}-22-(2-carboxyethyl)-32-[(1R)-1-hydroxyethyl]-4-methyl-19-(2-methylpropyl)-3,6,9,12,15,18,21,24,30,33,36-undecaoxo-7,13-bis(propan-2-yl)-27,28,40,41-tetrathia-2,5,8,11,14,17,20,23,31,34,37-undecaazabicyclo[14.13.13]dotetracontan-25-yl]carbamoyl}butanoic acid | [Molecular Formula]
C65H104N18O26S4 | [MDL Number]
MFCD33029246 | [MOL File]
467426-54-6.mol | [Molecular Weight]
1681.89 |
| Chemical Properties | Back Directory | [Boiling point ]
2120.0±65.0 °C(Predicted) | [density ]
1.47±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
3.61±0.21(Predicted) | [color ]
White to off-white | [Sequence]
Asn-Asp-Glu-Cys-Glu-Leu-Cys-Val-Asn-Val-Ala-Cys-Thr-Gly-Cys-Leu (Disulfide bridge: Cys4-Cys12; Cys7-Cys15) | [InChIKey]
NSPHQWLKCGGCQR-DLJDZFDSSA-N |
| Hazard Information | Back Directory | [Uses]
Plecanatide is used in the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. It works as a laxative by drawing water in to the gastrointestinal tract thereby softening stool and encouraging its natural passage. | [Brand name]
Trulance | [General Description]
Plecanatide is an oral guanylate cyclase-C agonist that is being developed by Synergy Pharmaceuticals for the treatment of gastrointestinal disorders, such as chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). It is a synthetic analogue of human uroguanylin, a 16 amino acid peptide that regulates ion and fluid transport in the gastrointestinal tract. In January 2017, plecanatide received its first global approval in the USA for the treatment of adult patients with CIC. Plecanatide is undergoing phase III investigation in IBS-C. | [Synthesis]
(1) Fmoc-Leu-resin is obtained by coupling the resin solid-phase carrier and Fmoc-Leu-OH in the presence of an activator system;
(2) coupling amino acids with N-terminal Fmoc protection and side-chain protection sequentially according to t | [Enzyme inhibitor]
This uroguanylin analogue (FW = 1681.90 g/mol; CAS 467426-54-6), also
known by the codename SP-304, binds to and activates guanylate cyclase-C
(GC-C) receptors (EC50 ≈ 0.3 μM) expressed on the epithelial cells lining
the gastrointestinal mucosa, stimulating cyclic GMP production, which in
turn sequentially activates protein kinase G-II and the chloride channel
known as the Cystic Fibrosis Transmembrane-conductance Regulator
(CFTR) to regulate ion and fluid transport, to promote epithelial cell
homeostasis, and to maintain barrier function in the GI mucosa. Plecanatide
is a hexadecapeptide that is structurally identical to uroguanylin, except for
an glutamate substitution at position-3. Oral treatment with plecanatide at a
dose range between 0.05-2.5 mg/kg per day is as effective as once-daily
treatment with 5-amino salicylic acid (100 mg/kg) or sulfasalazine (80
mg/kg). Amelioration of colitis by the treatment with plecanatide or
dolcanatide was not dose-dependent, most likely due to saturation of
available GC-C receptors. | [in vivo]
Plecanatide (0.5 and 2.5 mg/kg, p.o.) ameliorates spontaneous and chemically induced colitis after treatment for 7 days in BALB/c mice, and 14 days in TCRα-/- mice[1].
Plecanatide (0.005-5 mg/kg, once daily for 7 days) also shows anti-inflammatory activity in dextran sulfate sodium (DSS) and trinitrobenzene sulfonic (TNBS)-induced colitis in BDF-1 mice[1]. | Animal Model: | Female BALB/c mice (2-4 month old) are induced colitis by TNBS[1] | | Dosage: | 0, 0.5 and 2.5 mg/kg | | Administration: | P.o. for 7 days | | Result: | Effectively reduced colitis severity scores as compared to vehicle treatment. |
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