Plecanatide CAS 467426-54-6

Introduction：Basic information about Plecanatide CAS 467426-54-6, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Plecanatide Basic information

• Product Name: Plecanatide
• Synonyms: Plecanatide;ASN-ASP-GLU-CYS-GLU-LEU-CYS-VAL-ASN-VAL-ALA-CYS-THR-GLY-CYS-LEU(DISULFIDE BOND CYS1&CYS3,CYS2&CYS4);Plecanatide Impurtiy;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);Plecanatide impurity;Plecanatide USP/EP/BP;Prikanatide;ATCH(1-39)
• CAS: 467426-54-6
• MF: C65H104N18O26S4
• MW: 1681.89
• Mol File: 467426-54-6.mol

Plecanatide Chemical Properties

• Boiling point: 2120.0±65.0 °C(Predicted)
• density: 1.47±0.1 g/cm3(Predicted)
• pka: 3.61±0.21(Predicted)
• form: Solid
• 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)
• InChI: InChI=1S/C65H104N18O26S4/c1-25(2)15-34-55(98)80-41-24-113-110-21-38(58(101)77-37(65(108)109)16-26(3)4)71-44(87)20-69-62(105)50(30(10)84)83-61(104)40(78-51(94)29(9)70-63(106)48(27(5)6)81-57(100)35(18-43(68)86)76-64(107)49(28(7)8)82-60(41)103)23-112-111-22-39(59(102)73-32(53(96)75-34)11-13-45(88)89)79-54(97)33(12-14-46(90)91)72-56(99)36(19-47(92)93)74-52(95)31(66)17-42(67)85/h25-41,48-50,84H,11-24,66H2,1-10H3,(H2,67,85)(H2,68,86)(H,69,105)(H,70,106)(H,71,87)(H,72,99)(H,73,102)(H,74,95)(H,75,96)(H,76,107)(H,77,101)(H,78,94)(H,79,97)(H,80,98)(H,81,100)(H,82,103)(H,83,104)(H,88,89)(H,90,91)(H,92,93)(H,108,109)/t29-,30+,31-,32-,33-,34-,35-,36-,37-,38-,39-,40-,41-,48-,49-,50-/m0/s1
• InChIKey: NSPHQWLKCGGCQR-DLJDZFDSSA-N
• SMILES: S1C([H])([H])[C@@]2([H])C(N([H])[C@]([H])(C(N([H])[C@@]([H])(C([H])([H])C(N([H])[H])=O)C(N([H])[C@]([H])(C(N([H])[C@@]([H])(C([H])([H])[H])C(N([H])[C@]([H])(C(N([H])[C@]([H])(C(N([H])C([H])([H])C(N([H])[C@]([H])(C(N([H])[C@]([H])(C(=O)O[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)C([H])([H])S1)=O)=O)[C@@]([H])(C([H])([H])[H])O[H])=O)C([H])([H])SSC([H])([H])[C@@]([H])(C(N([H])[C@@]([H])(C([H])([H])C([H])([H])C(=O)O[H])C(N([H])[C@]([H])(C(N2[H])=O)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)=O)N([H])C([C@]([H])(C([H])([H])C([H])([H])C(=O)O[H])N([H])C([C@]([H])(C([H])([H])C(=O)O[H])N([H])C([C@]([H])(C([H])([H])C(N([H])[H])=O)N([H])[H])=O)=O)=O)=O)=O)C([H])(C([H])([H])[H])C([H])([H])[H])=O)=O)C([H])(C([H])([H])[H])C([H])([H])[H])=O

Safety Information

• Hazardous Substances Data: 467426-54-6(Hazardous Substances Data)

Plecanatide Usage And Synthesis

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 the peptide order of the main chain of pukanatide by solid-phase synthesis method, specifically including the following steps:

(i) using a deprotection solution comprising piperidine and DMF in a volume ratio of 1:4 to remove the Fmoc-protecting group on the Fmoc-Leu-resin to obtain the H-Leu-resin;

(ii) in the presence of a coupling agent system, H-Leu-resin and Fmoc-protected and side-chain-protected cysteine are coupled to obtain Fmoc-Cys(Trt)-Leu-resin;

(iii) Repeat steps ?? and ?? to couple amino acids sequentially according to the peptide sequence of the puccinatide main chain;

(3) Cleavage, liquid-phase cyclization;

(4) purification, lyophilization to obtain puccinatide; the sequence of said puccinatide is: H-Asn-Asp-Glu-Cys(1)-Glu-Leu-Cys(2)-Val-Asn-Val-Ala-Cys(1)-Thr-Gly-Cys(2)-Leu-OH.

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 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.