Plecanatide | CAS 467426-54-6 / 1075732-84-1 | Guanylate Cyclase-C Agonist (Research Use Only) | Knowlux

Product Description

Plecanatide, CAS 467426-54-6 (free peptide) / 1075732-84-1 (acetate salt), is a synthetic 16-amino-acid cyclic peptide analogue of uroguanylin, supplied by Knowlux for laboratory research use. The peptide is constrained by two intramolecular disulfide bridges and is a guanylate cyclase-C (GC-C) receptor agonist. The sequence is H-Asn-Asp-Glu-Cys-Glu-Leu-Cys-Val-Asn-Val-Ala-Cys-Thr-Gly-Cys-Leu-OH, with disulfide bridges between Cys4-Cys12 and Cys7-Cys15. The free peptide molecular formula is C65H104N18O26S4 and the molecular weight is 1681.89 g/mol; the acetate salt corresponds to C67H108N18O28S4 with a molecular weight of approximately 1741.94. Each lot is released with a lot-specific COA, MSDS and analytical traceability.

CAS and Salt Form Clarification: CAS 467426-54-6 is the free peptide registry and is the identifier applied to the active pharmaceutical ingredient across KEGG, PubChem, ChemicalBook, MedChemExpress, and Omizzur. CAS 1075732-84-1 is the acetate salt registry, confirmed by PubChem, MedChemExpress, GLPBIO, PeptideDB, and BOC Sciences. A substantial proportion of commercial listings use CAS 467426-54-6 under the product name "Plecanatide" while supplying the acetate salt, conflating the free peptide and salt registries. The molecular weight distinction is material: 1681.89 for the free peptide versus approximately 1741.94 for the acetate salt, a difference of approximately 60 g/mol. Knowlux specifies the salt basis, acetate content, and water content per lot on the COA. Buyers should confirm whether the quoted material is reported on a free-peptide or acetate-salt basis before procurement, particularly when calculating molarity from mass.

Structural Complexity Note: Plecanatide contains four cysteine residues forming two disulfide bonds (Cys4-Cys12 and Cys7-Cys15), a structural feature that is essential for GC-C receptor activation. Unlike the single-disulfide peptides in the Carbetocin and Atosiban families, Plecanatide is doubly constrained, and correct disulfide pairing is a critical quality attribute that cannot be inferred from a single HPLC purity figure. Buyers should request disulfide mapping or co-elution data against a characterized reference standard where receptor activity is the readout.

Product Parameters

Product Details

1. Overview

Plecanatide is a 16-residue synthetic analogue of uroguanylin, an endogenous peptide hormone that regulates intestinal fluid and electrolyte homeostasis. The analogue was engineered for oral activity and stability relative to the native peptide. Plecanatide acts as an agonist at guanylate cyclase-C (GC-C), a receptor expressed on the luminal surface of intestinal enterocytes. KEGG classifies Plecanatide under ATC code A06AX07 as a peristaltic accelerator and enterotoxin receptor agonist, with the target annotated as GUCY2C. Activation of GC-C elevates intracellular and extracellular cyclic GMP, which in turn activates the CFTR chloride channel and stimulates chloride and bicarbonate secretion into the intestinal lumen, increasing intestinal fluid and accelerating transit. In clinical medicine, Plecanatide is approved for chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). The material supplied under this specification is research-grade and is not intended for human administration. Knowlux supplies this compound strictly for laboratory investigation of GC-C signaling, intestinal ion transport, and mucosal biology.

2. Receptor Pharmacology and Functional Profile

Plecanatide binds and activates GC-C with high potency. Omizzur reports an EC50 of 190 nM in T84 cells for GC-C-mediated signaling. The peptide also exhibits anti-inflammatory activity in mouse colitis models, consistent with the broader role of the GC-C/cGMP axis in intestinal immune regulation. The pharmacological profile of Plecanatide overlaps with that of linaclotide (another GC-C agonist in this catalogue), but the two peptides differ in sequence, disulfide connectivity, and clinical pharmacology: linaclotide is a 14-residue peptide with three disulfide bridges, whereas Plecanatide is a 16-residue peptide with two disulfide bridges. The lower diarrheal rate observed for Plecanatide relative to linaclotide in clinical trials has been attributed in part to differences in pH-dependent receptor engagement and intestinal regional selectivity, although the mechanistic basis remains an active area of research. These descriptions are derived from published research and are provided for scientific reference only.

3. Research Applications

Published pharmacological characterizations and documented protocols describe the following research applications:

• GC-C receptor binding and functional assays (cGMP accumulation in T84 and other intestinal cell models)

• Intestinal chloride and bicarbonate secretion studies

• Intestinal motility and transit research models

• Anti-inflammatory signaling in colitis and mucosal immunity models

• Comparative pharmacology of GC-C agonists (Plecanatide versus linaclotide)

• Disulfide-rich peptide folding and analytical characterization

• Reference standard development for HPLC and LC-MS analytical methods

These descriptions are derived from published research and are provided for scientific reference only. They do not constitute clinical guidance or dosing recommendations.

Quality Control

Solubility and Handling

Solubility: Plecanatide solubility is the most inconsistently reported parameter across supplier sources, and the divergence is larger than for most peptides in this catalogue. At the high-solubility end, BenchChem states that Plecanatide is soluble in water, phosphate-buffered saline (PBS), and DMSO, and Tongze Biotechnology describes it as highly soluble in water and aqueous buffer, soluble in dilute acetic acid and DMSO. Selleck lists water solubility as "<=5.0% mg/mL" (i.e., slightly soluble or insoluble) and does not report a numeric DMSO value in the visible excerpt. MedChemExpress reports DMSO solubility of 3 mg/mL (1.72 mM) requiring sonication. Cayman Chemical lists DMF 1 mg/mL, DMSO 3 mg/mL, and PBS (pH 7.2) 10 mg/mL for the acetate salt. An Ambeed listing reports DMSO solubility of 100 mg/mL with sonication, but this figure is accompanied by a note that hygroscopic DMSO can significantly affect solubility and that freshly opened DMSO should be used, which suggests the high value may reflect a specific dissolution protocol rather than a general property of the peptide. For practical stock preparation, DMSO at 3 mg/mL is the most consistently supported numeric value across the principal research-grade suppliers; PBS at 10 mg/mL is supported by Cayman for the acetate salt. Aqueous buffers may require sonication, and the pH-dependent solubility of this acidic peptide (multiple Asp and Glu residues) should be evaluated empirically on the specific lot and buffer system. Prepare solutions fresh and avoid prolonged storage in aqueous media; BenchChem notes that aqueous Plecanatide solutions are not recommended for storage beyond one day.

Handling Precautions: Use powder-handling containment (glove box or fume hood with particulate control). Avoid inhalation of fine powder. Wear nitrile gloves, lab coat, and eye protection. ChemicalBook assigns GHS07 (Warning, H302-H315-H319-H335) for CAS 467426-54-6. The disulfide bridges are sensitive to reducing agents; avoid contact with dithiothreitol (DTT) or mercaptoethanol during handling. Omizzur recommends centrifuging the vial briefly before opening to gather any lyophilized powder adhering to the cap or walls.

Storage and Stability

Documentation Support

Per lot: COA, MSDS, certificate of origin, HPLC chromatogram, and mass spectrometry data. Disulfide connectivity data, acetate content, water content, peptide content, and endotoxin data available on request. Custom specifications and third-party inspection can be arranged on a project basis.

About Knowlux

Knowlux Biotechnology is a GMP-oriented manufacturer and supplier of peptides, APIs and fine-chemical research compounds, operating from Hubei, China. We serve research groups, CDMOs and distributors in more than 40 countries, and support contract synthesis, custom packaging and technical documentation requests.

Compliance Statement

FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE.

This product is supplied for laboratory research use only. It is not for human or animal administration, not for diagnostic or therapeutic use, not for retail sale, and not for personal use. Plecanatide is an approved medicinal product in certain jurisdictions for specific clinical indications (chronic idiopathic constipation and IBS-C); however, the material offered under this specification is research-grade and is not intended for clinical use. The purchaser is responsible for verifying product specifications against their specific research requirements and for compliance with all applicable institutional, local, and national regulations governing research chemical acquisition, storage, and use. Research context statements are for scientific reference only and do not constitute medical advice, promotional claims, or dosing guidance.

Data Verification Notes: The free peptide molecular formula C65H104N18O26S4 and molecular weight 1681.89 are confirmed by KEGG (exact mass 1680.6252, mol weight 1681.90), ChemicalBook (1681.89), Omizzur (1681.89), and ChemSpider (average mass 1681.887). The sequence H-Asn-Asp-Glu-Cys-Glu-Leu-Cys-Val-Asn-Val-Ala-Cys-Thr-Gly-Cys-Leu-OH with disulfide bridges Cys4-Cys12 and Cys7-Cys15 is confirmed by KEGG, Omizzur, and Adooq. The acetate salt CAS 1075732-84-1, formula C67H108N18O28S4, and molecular weight 1741.94 are confirmed by PubChem (1741.9), MedChemExpress, GLPBIO, PeptideDB, and InvivoChem. Solubility values are reported with their source conditions rather than reconciled into a single figure because the underlying measurements span the full range from "insoluble" to "100 mg/mL" and reflect different salt forms, dissolution techniques, and buffer systems. The GHS07 classification (H302-H315-H319-H335) is from ChemicalBook. Storage guidance divergence (aqueous versus DMSO solution stability) is reported as-is; the BenchChem recommendation against aqueous storage beyond one day is presented as the most conservative solution-handling guidance.

Formatting Note: All formulas, sequences, and comparison operators use plain ASCII notation to prevent character corruption on the platform. Section headings, table alignment, and spacing follow the approved product detail pattern. No trailing spaces or non-breaking characters are used; tables use consistent pipe alignment.