| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
guanylate cyclase-C receptor, T84 cells ( EC50 = 190 nM )
Plecanatide acetate targets the guanylate cyclase-C (GC-C) receptor, which is a transmembrane receptor expressed on the luminal surface of intestinal epithelial cells. By binding to and activating the GC-C receptor, plecanatide stimulates the production of intracellular cyclic GMP (cGMP). The increase in cGMP activates protein kinase G (PKG) and the cystic fibrosis transmembrane conductance regulator (CFTR), leading to the efflux of chloride and bicarbonate ions into the intestinal lumen. This increases fluid secretion, accelerates gastrointestinal transit, and alleviates constipation. In addition, the increase in cGMP inhibits pain signaling in the gut by reducing the activity of nociceptive neurons, which may contribute to the compound's efficacy in IBS-C. The compound's anti-inflammatory activity is mediated by the activation of the GC-C receptor on immune cells and the suppression of pro-inflammatory cytokine production. Plecanatide acetate is a potent and selective GC-C receptor agonist with high affinity and efficacy. |
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| ln Vitro |
Plecanatide (1 nM–10 μM) stimulates cGMP synthesis in a dose-dependent manner with an EC50 of 190 nM by activating the GC-C receptor in T84 cells[1].
In vitro studies have demonstrated that plecanatide acetate is a potent activator of the GC-C receptor. In T84 cells (a human colonic epithelial cell line), plecanatide acetate activates GCC with an EC₅₀ of 190 nM, as measured by the accumulation of cGMP. The compound's efficacy is comparable to that of the endogenous ligand uroguanylin. In addition to its effects on cGMP production, plecanatide acetate has been shown to inhibit the growth of colorectal cancer cells in vitro, suggesting potential anticancer activity. The compound's anti-inflammatory effects have been demonstrated in macrophage cultures, where it reduces the production of TNF-α, IL-1β, and other pro-inflammatory cytokines. In cell viability assays, plecanatide acetate does not exhibit significant cytotoxicity at concentrations up to 100 µM, indicating a favorable safety profile for in vitro applications. |
| ln Vivo |
Plecanatide (0.5 and 2.5 mg/kg, p.o.) improves colitis that is chemically and spontaneously induced in BALB/c mice after 7 days of treatment, and in TCRα-/- mice, it takes 14 days[1].
Plecanatide (0.005–5 mg/kg, once daily for seven days) also exhibits anti-inflammatory properties in BDF-1 mice that have colitis induced by trinitrobenzene sulfonic (TNBS) and dextran sulfate sodium (DSS)[1]. In vivo studies have demonstrated the efficacy of plecanatide acetate in animal models of constipation and colitis. In rodent models of constipation, oral administration of plecanatide acetate at doses of 0.1-10 mg/kg increases fecal output, reduces fecal hardness, and accelerates gastrointestinal transit. The compound's effects are dose-dependent and are mediated by the activation of the GC-C receptor. In mouse models of colitis, plecanatide acetate reduces colonic inflammation, mucosal damage, and the production of pro-inflammatory cytokines. The compound's anti-inflammatory effects are associated with the activation of the GC-C receptor on immune cells and the suppression of NF-κB signaling. In clinical trials, plecanatide has been shown to be effective in the treatment of chronic idiopathic constipation and IBS-C, with significant improvements in stool frequency, stool consistency, and abdominal pain. The compound is well-tolerated, with the most common adverse effect being diarrhea, which is related to its mechanism of action. |
| Enzyme Assay |
For in vitro cell-based assays, plecanatide acetate is typically evaluated for its ability to activate GC-C receptors and stimulate cGMP production in T84 cells or other GC-C-expressing cell lines. Cells are seeded in 6- or 12-well plates and treated with the compound at concentrations of 0.01-1000 nM for 30-60 minutes. The accumulation of cGMP is measured using a competitive ELISA or a radioimmunoassay. The EC₅₀ for cGMP production is determined from dose-response curves. For anti-inflammatory studies, macrophages or other immune cells are stimulated with LPS in the presence or absence of plecanatide acetate, and the production of TNF-α, IL-1β, and other cytokines is measured by ELISA. For cell proliferation assays, cancer cells are treated with the compound for 24-72 hours, and cell viability is determined using MTT or CellTiter-Glo assays. All experiments include appropriate positive and negative controls, and results are expressed as mean ± standard deviation from at least three independent experiments.
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| Animal Protocol |
Female BALB/c mice (2-4 month old) are induced colitis by TNBS
0, 0.5 and 2.5 mg/kg P.o. for 7 days For in vivo animal experiments, plecanatide acetate is typically administered orally to mice or rats. For constipation models, animals are fasted overnight and then treated with the compound at doses of 0.1-10 mg/kg. Fecal output and stool consistency are measured over 4-6 hours. Gastrointestinal transit is assessed by measuring the distance traveled by a fluorescent or radioactive marker. For colitis models, mice are treated with dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis, and plecanatide acetate is administered daily for 7-14 days. Colonic inflammation is assessed by measuring disease activity index (DAI), colon length, histological scoring, and cytokine levels. For pharmacokinetic studies, blood samples are collected at various time points, and plasma concentrations of plecanatide are measured by LC-MS/MS. All animal procedures are conducted in accordance with institutional guidelines for the care and use of laboratory animals. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of plecanatide acetate have been conducted in animals and humans. The compound has a molecular weight of approximately 1741.9-1741.94 g/mol and a molecular formula of C₆₇H₁₀₈N₁₈O₂₈S₄ (acetate salt). Following oral administration, plecanatide is minimally absorbed from the gastrointestinal tract, with less than 1% of the dose reaching the systemic circulation. The compound acts locally on the GC-C receptors in the intestinal epithelium, which is consistent with its mechanism of action and its favorable safety profile. The compound is metabolized in the gastrointestinal tract by proteolytic enzymes, and the metabolites are excreted in feces. The compound is stable when stored as a powder at -20°C or 4°C, protected from light and moisture. For in vivo administration, plecanatide acetate can be formulated in water, saline, or other suitable vehicles.
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| Toxicity/Toxicokinetics |
Plecanatide acetate has a favorable safety profile based on clinical trials and preclinical studies. The compound is well-tolerated at therapeutic doses, with diarrhea being the most common adverse effect. In preclinical toxicology studies, the compound has been shown to be non-toxic at doses up to 100 mg/kg/day in rodents. No significant genotoxicity, carcinogenicity, or reproductive toxicity has been reported. The compound's minimal systemic absorption contributes to its favorable safety profile. As with all research chemicals, appropriate safety precautions should be taken when handling plecanatide acetate, including the use of personal protective equipment. The compound is for research use only and is not intended for human therapeutic use outside of its approved clinical indications.
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| References |
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| Additional Infomation |
Plecanatide acetate is an FDA-approved drug for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. It is also known as plecanatide acetate and is marketed under various brand names. The compound has a molecular formula of C₆₇H₁₀₈N₁₈O₂₈S₄ (acetate salt) and a molecular weight of approximately 1741.9-1741.94 g/mol. Plecanatide acetate is a synthetic peptide analog of uroguanylin that acts as an orally active GC-C receptor agonist. The compound is used for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation, and it also shows anti-inflammatory activity. Plecanatide acetate is available from various research chemical suppliers for non-clinical studies, with purities typically ≥95% (HPLC). Storage recommendations include keeping the compound in a tightly sealed container, protected from light and moisture, at -20°C or 4°C.
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| Molecular Formula |
C67H108N18O28S4
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|---|---|
| Molecular Weight |
1741.9382314682
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| Exact Mass |
1740.65
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| CAS # |
1075732-84-1
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| Related CAS # |
Plecanatide; 467426-54-6
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| PubChem CID |
168011839
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
24
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| Hydrogen Bond Acceptor Count |
33
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| Rotatable Bond Count |
28
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| Heavy Atom Count |
117
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| Complexity |
3520
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| Defined Atom Stereocenter Count |
15
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| SMILES |
C(=O)(O)C.N([C@H]1CSSC[C@H]2C(N[C@H](C(NCC(N[C@@H](CSSC[C@@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N2)=O)C)=O)C(C)C)=O)CC(=O)N)=O)C(C)C)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC1=O)C(=O)N[C@H](C(=O)O)CC(C)C)=O)=O)[C@H](O)C)=O)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](N)CC(=O)N
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| InChi Key |
NTDAGCOLNINBIG-QDPGAZTQSA-N
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| InChi Code |
InChI=1S/C65H104N18O26S4.C2H4O2/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;1-2(3)4/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);1H3,(H,3,4)/t29-,30+,31-,32-,33-,34-,35-,36-,37-,38-,39-,40-,41-,48?,49-,50-;/m0./s1
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| Chemical Name |
acetic acid;(2S)-2-[[(1R,4S,10S,13S,16R,19S,22S,25R,32S,38R)-10-(2-amino-2-oxoethyl)-25-[[(2S)-4-carboxy-2-[[(2S)-3-carboxy-2-[[(2S)-2,4-diamino-4-oxobutanoyl]amino]propanoyl]amino]butanoyl]amino]-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-di(propan-2-yl)-27,28,40,41-tetrathia-2,5,8,11,14,17,20,23,31,34,37-undecazabicyclo[14.13.13]dotetracontane-38-carbonyl]amino]-4-methylpentanoic acid
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| Synonyms |
Plecanatide acetate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5741 mL | 2.8704 mL | 5.7407 mL | |
| 5 mM | 0.1148 mL | 0.5741 mL | 1.1481 mL | |
| 10 mM | 0.0574 mL | 0.2870 mL | 0.5741 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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