Plecanatide
Also known as: Trulance (brand) · SP-304
Plecanatide is a synthetic 16-amino-acid peptide analog of human uroguanylin, an endogenous intestinal hormone, and activates the same guanylate cyclase-C (GC-C) receptor targeted by Linaclotide, also built on this site. At Verified Peptides, we want to note the key structural distinction between these two related GC-C agonists: Plecanatide is specifically modeled on uroguanylin alone (16 residues, two disulfide bonds), while Linaclotide's design draws on both guanylin and uroguanylin (14 residues, three disulfide bonds) — different specific engineering paths to activating the same therapeutic target. FDA-approved in January 2017 (as Trulance) for chronic idiopathic constipation, with irritable bowel syndrome with constipation added later, Plecanatide's real Phase III trial (Miner et al. 2017, PMID 28169285, American Journal of Gastroenterology) in 1,394 patients found durable responder rates of 19.5-21.0% versus 10.2% with placebo (p<0.001 for both doses). Like Linaclotide, Plecanatide is an oral peptide specifically designed for minimal systemic absorption, acting locally within the intestinal lumen. Research-grade material sold here is a separate product intended solely for laboratory research.
What is Plecanatide?
Plecanatide is a synthetic 16-amino-acid peptide (a hexadecapeptide) designed as a structural analog of human uroguanylin, one of two endogenous intestinal peptide hormones (alongside guanylin) that activate the guanylate cyclase-C (GC-C) receptor on intestinal epithelial cells. This places Plecanatide in the same general therapeutic class as Linaclotide, also built on this site, though the two compounds differ in their specific design lineage and structure: Plecanatide is modeled specifically on uroguanylin (16 residues, cyclized via two disulfide bonds bridging positions 4-12 and 7-15), while Linaclotide's structure draws on both guanylin and uroguanylin (14 residues, cyclized via three disulfide bonds).
At Verified Peptides, we want to note that Plecanatide was developed by Synergy Pharmaceuticals (later acquired by Bausch Health) under the research code SP-304, and received FDA approval in January 2017 (as Trulance) for chronic idiopathic constipation in adults, with an indication expansion for irritable bowel syndrome with constipation (IBS-C) added later — largely paralleling Linaclotide's own approved indications, though as a separately developed, distinctly structured compound rather than a generic or biosimilar version of Linaclotide.
Chemically, Plecanatide has molecular formula C65H104N18O26S4, molecular weight approximately 1682 g/mol (independently cross-calculated atom-by-atom from the formula, matching literature figures closely), CAS number 467426-54-6. Like Linaclotide, Plecanatide is administered as an oral tablet and is specifically designed for minimal systemic absorption, acting locally within the intestinal lumen rather than through systemic circulation — the same distinctive pharmacokinetic profile discussed in more depth in this site's Linaclotide profile.
We independently cross-calculated Plecanatide's molecular weight atom-by-atom from its formula (65 carbon at 12.011, 104 hydrogen at 1.008, 18 nitrogen at 14.007, 26 oxygen at 15.999, and 4 sulfur at 32.06), arriving at approximately 1681.9 g/mol, closely matching the commonly reported 1682 g/mol figure, giving us confidence in these chemical identifiers.
Key Benefits & Mechanisms
Mechanism of action
Plecanatide activates guanylate cyclase-C (GC-C) receptors on the luminal surface of intestinal epithelial cells, the same receptor targeted by endogenous uroguanylin and guanylin, and by Linaclotide, also built on this site. GC-C activation increases intracellular cyclic guanosine monophosphate (cGMP), which stimulates chloride and bicarbonate secretion into the intestinal lumen primarily through the cystic fibrosis transmembrane conductance regulator (CFTR) channel, drawing water into the lumen and increasing intestinal fluid content, which softens stool and accelerates intestinal transit.
A notable pharmacological distinction between Plecanatide and Linaclotide relates to their respective activation profiles across the physiological pH range of the gastrointestinal tract: Plecanatide, as a uroguanylin analog, has been studied for pH-dependent activation more closely resembling native uroguanylin's own activity pattern (which is thought to be more active in the relatively neutral-to-alkaline environment of the distal small intestine and colon), a design rationale distinct from Linaclotide's dual guanylin/uroguanylin-inspired structure. We want to note that the clinical significance of this specific pH-activation distinction, relative to the two compounds' overall clinical efficacy, remains an area of ongoing research and is not something we can characterize as a definitively established clinical difference based on the sources reviewed for this profile.
As with Linaclotide, cGMP generated at the intestinal luminal surface following Plecanatide's GC-C activation has also been proposed to reduce visceral pain-sensing afferent nerve activity, providing a mechanistic basis for symptom improvement beyond stool frequency alone in patients whose constipation is accompanied by abdominal discomfort — a shared secondary mechanism across both GC-C agonist compounds in this catalog, reflecting the fact that this pain-modulating effect appears to be a property of GC-C pathway activation generally rather than a feature unique to either compound's specific sequence.
Research Summary
At Verified Peptides, we think Plecanatide has a real, rigorous, and directly comparable evidence base to Linaclotide's, reflecting its status as a separately developed but similarly mechanistically-grounded GC-C agonist. The pivotal citation is Miner et al. (2017, American Journal of Gastroenterology, PMID 28169285, volume 112, issue 4, pages 613-621), a Phase III, multicenter, double-blind, placebo-controlled trial randomizing 1,394 patients with chronic idiopathic constipation to receive plecanatide (3 mg or 6 mg) or placebo orally once daily for 12 weeks. Both plecanatide doses produced significantly greater durable overall complete spontaneous bowel movement (CSBM) responder rates (21.0% for 3 mg, 19.5% for 6 mg) compared to placebo (10.2%), with p less than 0.001 for both doses, alongside significant improvement in constipation-related symptoms and a reported low rate of adverse events.
We want to note that Plecanatide's overall responder-rate magnitude in this trial is broadly comparable to, though numerically somewhat different from, the responder-rate figures reported in Linaclotide's own pivotal trials discussed on this site's Linaclotide profile — though we want to be direct that these are different trials, using different specific endpoints and patient populations, and we are not presenting this as a validated head-to-head efficacy comparison, since no direct randomized comparative trial between Plecanatide and Linaclotide was identified during this research process. Both compounds' pivotal trials used broadly similar durable-responder-style primary endpoints, reflecting a general regulatory convergence in how chronic idiopathic constipation trials have come to be designed and evaluated across this drug class, even though the two specific trials were conducted independently by different manufacturers with their own separate patient populations, follow-up periods, and statistical analysis plans. Researchers interested in a rigorous efficacy comparison between these two GC-C agonists should look for dedicated head-to-head trial data specifically, rather than informally comparing each compound's separate placebo-controlled trial results.
At Verified Peptides, we sell research-grade Plecanatide exclusively for laboratory research, and we think this compound, alongside Linaclotide, illustrates how a single validated molecular target (the GC-C receptor) can support multiple independently developed, structurally distinct therapeutic peptides pursuing the same general clinical goal through different specific design lineages.
Common Stacks
Lesser-Known Facts About Plecanatide
Uroguanylin and guanylin, the two endogenous hormones underlying Plecanatide's and Linaclotide's respective designs, are both part of a broader peptide family that also includes the heat-stable enterotoxins produced by certain pathogenic Escherichia coli strains, meaning both Plecanatide and Linaclotide represent controlled pharmaceutical applications of the same fundamental GC-C receptor pathway that certain bacterial toxins exploit to cause diarrheal illness — a shared origin point for this entire drug class rather than something unique to either individual compound.
Plecanatide's development under the research code SP-304 by Synergy Pharmaceuticals, and its subsequent acquisition alongside the rest of Synergy's assets by Bausch Health, reflects a common pattern in specialty pharmaceutical development, where a smaller biotechnology company develops and gains initial approval for a novel compound before a larger pharmaceutical company acquires the rights for continued commercialization and further indication expansion.
The specific two-disulfide-bond (versus Linaclotide's three-disulfide-bond) cyclization pattern in Plecanatide reflects the fact that native uroguanylin itself has a somewhat different cysteine spacing and disulfide bonding pattern than native guanylin, meaning the structural difference between Plecanatide and Linaclotide traces back to genuine differences between their respective endogenous hormone templates, not merely to different arbitrary engineering choices by their respective development teams.
Purity & Sourcing Considerations
At Verified Peptides, we require independent third-party HPLC purity testing and mass spectrometry identity confirmation for every batch of research-grade Plecanatide we offer, with a Certificate of Analysis (COA) available for each lot. Given Plecanatide's two-disulfide-bond cyclic structure, correct formation of both disulfide bridges should be confirmed as part of identity testing, since incomplete or incorrect cyclization would represent a structurally distinct, likely non-functional molecule.
We source exclusively from manufacturers operating under Good Manufacturing Practice (GMP)-aligned quality systems, and every lot is independently verified rather than accepted solely on a supplier's internal documentation. Researchers should always request and review the specific COA for the lot they receive, confirming purity percentage and molecular identity before use in any experimental protocol.
Storage & Stability
Lyophilized Plecanatide is stable when stored at -20°C, protected from light and moisture. At Verified Peptides, we ship lyophilized peptide with appropriate cold-chain packaging to preserve stability in transit.
Once reconstituted, solution should be stored refrigerated at 2–8°C and used within the timeframe indicated on the product's documentation, avoiding repeated freeze-thaw cycles. As a peptide with two disulfide bonds, Plecanatide may be sensitive to reducing conditions that could disrupt its cyclic structure, so researchers should follow lot-specific handling guidance to preserve structural integrity.
Frequently asked questions about Plecanatide
What is Plecanatide and how does it differ from Linaclotide?
Both are synthetic guanylate cyclase-C (GC-C) receptor agonists, but Plecanatide is specifically modeled on the endogenous hormone uroguanylin alone (16 residues, two disulfide bonds), while Linaclotide draws on both guanylin and uroguanylin (14 residues, three disulfide bonds) — separately developed compounds targeting the same receptor through different specific designs.
Is Plecanatide FDA approved?
Yes, since January 2017 (as Trulance), for chronic idiopathic constipation in adults, with irritable bowel syndrome with constipation (IBS-C) added as an indication later.
What evidence supports Plecanatide's efficacy?
A Phase III trial (Miner et al. 2017, PMID 28169285) in 1,394 patients with chronic idiopathic constipation found durable responder rates of 19.5-21.0% with plecanatide versus 10.2% with placebo, both statistically significant (p<0.001).
What is the mechanism of action of Plecanatide?
Plecanatide activates guanylate cyclase-C receptors on intestinal epithelial cells, increasing cGMP, which stimulates chloride and bicarbonate secretion via the CFTR channel, drawing water into the intestinal lumen and accelerating transit.
Is there direct clinical trial evidence comparing Plecanatide to Linaclotide head-to-head?
We did not identify a dedicated randomized head-to-head trial comparing the two compounds directly during this research process. Each has its own separate placebo-controlled trial data, and researchers should seek dedicated comparative trial data rather than informally comparing the two compounds' separate trial results.
Does Plecanatide have minimal systemic absorption like Linaclotide?
Yes. Like Linaclotide, Plecanatide is an oral peptide specifically designed to act locally within the intestinal lumen with minimal systemic absorption, rather than requiring systemic bioavailability to reach its target tissue.
Is Plecanatide related to any bacterial toxins?
The GC-C receptor Plecanatide activates is the same receptor targeted by heat-stable enterotoxins from certain pathogenic E. coli strains that cause diarrheal illness, a shared origin point for the entire GC-C agonist drug class, including both Plecanatide and Linaclotide.
Why does Plecanatide have a different disulfide-bonding pattern than Linaclotide?
The difference traces back to their respective endogenous hormone templates: native uroguanylin (Plecanatide's model) has a different cysteine spacing and disulfide bonding pattern than native guanylin, which contributes to Linaclotide's design. The structural difference reflects genuine biological differences between these two related hormones, not arbitrary engineering choices.
Who originally developed Plecanatide?
Synergy Pharmaceuticals developed Plecanatide under the research code SP-304 and secured its original FDA approval. Synergy's assets, including Plecanatide, were later acquired by Bausch Health, which continues to market it as Trulance.
Legal & research status: Plecanatide is FDA-approved (as Trulance, since January 2017) for chronic idiopathic constipation and irritable bowel syndrome with constipation in adults. Material sold as a research compound is offered strictly for laboratory and research use, not for human consumption or therapeutic use.