Plecanatide
Identification
- Summary
Plecanatide is a laxative used to treat chronic idiopathic constipation and IBS with constipation.
- Brand Names
- Trulance
- Generic Name
- Plecanatide
- DrugBank Accession Number
- DB13170
- Background
Plecanatide is a drug approved in January 2017 by the FDA for the treatment of chronic idiopathic constipation (CIC). It should not be used in children less than six years of age, and should be avoided in patients six years to 18 years of age
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Plecanatide (DB13170)
- Weight
- Average: 1681.89
Monoisotopic: 1680.625200237 - Chemical Formula
- C65H104N18O26S4
- Synonyms
- Guanilib
- Plecanatide
Pharmacology
- Indication
Plecanatide stimulates intestinal fluid secretions in the gastrointestinal tract to support regular bowel function. Plecanatide, taken orally once daily, works locally in the upper GI tract to stimulate secretion of intestinal fluid and support regular bowel function.
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- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Food Effect Subjects who received either a low-fat, low calorie (LF-LC) meal or a high fat, high calorie (HF-HC) meal reported looser stools than fasted subjects up to 24 hours after a single dose of 9 mg (3 times the recommended dose). In clinical studies, Plecanatide was administered with or without food.
- Mechanism of action
Guanylate cyclase C (GC-C) agonist Plecanatide and its active metabolite bind to GC-C and act locally on the luminal surface of intestinal epithelial cells; GC-C activation leads to increased cyclic guanosine monophosphate (cGMP), which, in turn, stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly by activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit. In animal models, plecanatide has been shown to increase fluid secretion into the gastrointestinal (GI) tract, accelerate intestinal transit, and cause changes in stool consistency. In an animal model of visceral pain, plecanatide reduced abdominal muscle contractions, a measure of intestinal pain. The mechanism has not been studied.
Target Actions Organism AGuanylate cyclase soluble subunit alpha-2 agonistHumans - Absorption
Plecanatide is minimally absorbed with negligible systemic availability following oral administration. Concentrations of plecanatide and its active metabolite in plasma are below the limit of quantitation after an oral dose of 3 mg. Therefore, standard pharmacokinetic parameters such as AUC, maximum concentration (Cmax), and half-life (t½) cannot be calculated.
- Volume of distribution
Concentrations of plecanatide and its active metabolite in plasma are below the limit of quantitation after an oral dose of 3 mg. Therefore, the volume of distribution can not be calculated.
- Protein binding
Plecanatide exhibits little to no binding to human serum albumin or human α-1-acid glycoprotein.
- Metabolism
Plecanatide is metabolized in the GI tract to an active metabolite by loss of the terminal leucine moiety. Both plecanatide and the metabolite are proteolytically degraded within the intestinal lumen to smaller peptides and naturally occurring amino acids.
- Route of elimination
No excretion studies have been conducted in humans. Plecanatide and its active metabolite are not measurable in plasma following administration of the recommended clinical doses.
- Half-life
half-life (t½) cannot be calculated due to negligible systemic absorbance
- Clearance
No excretion studies have been conducted in humans.
- Adverse Effects
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Single oral doses of plecanatide at 0.5 mg/kg and 10 mg/kg caused mortality in young juvenile mice on postnatal days 7 and 14, respectively (human age equivalent of approximately 1 month to less than 2 years).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Plecanatide. Aclidinium The therapeutic efficacy of Plecanatide can be decreased when used in combination with Aclidinium. Alfentanil The therapeutic efficacy of Plecanatide can be decreased when used in combination with Alfentanil. Alloin The risk or severity of adverse effects can be increased when Plecanatide is combined with Alloin. Amantadine The therapeutic efficacy of Plecanatide can be decreased when used in combination with Amantadine. Amiloride The risk or severity of adverse effects can be increased when Amiloride is combined with Plecanatide. Amiodarone The therapeutic efficacy of Plecanatide can be decreased when used in combination with Amiodarone. Amitriptyline The therapeutic efficacy of Plecanatide can be decreased when used in combination with Amitriptyline. Amlodipine The therapeutic efficacy of Plecanatide can be decreased when used in combination with Amlodipine. Amobarbital The therapeutic efficacy of Plecanatide can be decreased when used in combination with Amobarbital. 
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- Take with or without food.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Trulance Tablet Oral Bausch Health, Canada Inc. Not applicable Not applicable Canada 
Trulance Immediate release Tablet 3 mg/1 Oral Salix Pharmaceuticals Inc. 2017-02-21 Not applicable US 
Trulance Immediate release Tablet 3 mg/1 Oral Synergy Pharmaceuticals Inc. 2017-02-21 Not applicable US
Categories
- ATC Codes
- A06AX07 — Plecanatide
- Drug Categories
- Alimentary Tract and Metabolism
- Amino Acids, Peptides, and Proteins
- Drugs for Constipation
- Enzyme Activators
- Gastrointestinal Agents
- Guanylate Cyclase Activators
- Guanylate Cyclase-C Agonist
- Guanylyl Cyclase C Agonists
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Laxatives
- Peptide Hormones
- Peptides
- Receptors, Guanylate Cyclase-Coupled, agonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
- Kingdom
- Organic compounds
- Super Class
- Organic Polymers
- Class
- Polypeptides
- Sub Class
- Not Available
- Direct Parent
- Polypeptides
- Alternative Parents
- Cyclic peptides / Glutamic acid and derivatives / Asparagine and derivatives / Aspartic acid and derivatives / Leucine and derivatives / Tetracarboxylic acids and derivatives / N-acyl-L-alpha-amino acids / Macrolactams / Alpha amino acid amides / N-acyl amines show 12 more
- Substituents
- Alcohol / Aliphatic heteropolycyclic compound / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Asparagine or derivatives / Aspartic acid or derivatives / Azacycle show 31 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 7IK8Z952OK
- CAS number
- 467426-54-6
- InChI Key
- NSPHQWLKCGGCQR-DLJDZFDSSA-N
- 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
- IUPAC Name
- (4S)-4-{[(2S)-2-{[(2S)-2-amino-1-hydroxy-3-(C-hydroxycarbonimidoyl)propylidene]amino}-3-carboxy-1-hydroxypropylidene]amino}-4-{[(1R,4S,7S,10S,13S,16R,19S,22S,25R,32S,38R)-38-{[(1S)-1-carboxy-3-methylbutyl]-C-hydroxycarbonimidoyl}-22-(2-carboxyethyl)-3,6,9,12,15,18,21,24,30,33,36-undecahydroxy-10-[(C-hydroxycarbonimidoyl)methyl]-32-[(1R)-1-hydroxyethyl]-4-methyl-19-(2-methylpropyl)-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]dotetraconta-2,5,8,11,14,17,20,23,30,33,36-undecaen-25-yl]-C-hydroxycarbonimidoyl}butanoic acid
- SMILES
- [H][C@@]12CSSC[C@H](NC(=O)CNC(=O)[C@@]([H])(NC(=O)[C@]([H])(CSSC[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC2=O)C(C)C)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O
References
- General References
- Thomas RH, Luthin DR: Current and emerging treatments for irritable bowel syndrome with constipation and chronic idiopathic constipation: focus on prosecretory agents. Pharmacotherapy. 2015 Jun;35(6):613-30. doi: 10.1002/phar.1594. Epub 2015 May 27. [Article]
- Drug Information [Link]
- Medscape [Link]
- FDA label [Link]
- External Links
- PubChem Compound
- 70693500
- PubChem Substance
- 347829276
- ChemSpider
- 28530494
- 1873752
- ChEMBL
- CHEMBL2103867
- Wikipedia
- Plecanatide
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Chronic idiopathic constipation (CIC) 3 3 Completed Treatment Irritable Bowel Syndrome (IBS) 1 3 Completed Treatment Irritable Bowel Syndrome Characterized by Constipation 2 2 Completed Treatment Chronic idiopathic constipation (CIC) 1 2 Completed Treatment Irritable Bowel Syndrome Characterized by Constipation 1 2 Recruiting Treatment Constipation-predominant Irritable Bowel Syndrome (IBS-C) 1 2, 3 Completed Treatment Chronic idiopathic constipation (CIC) 1 Not Available Completed Not Available Chronic idiopathic constipation (CIC) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet Oral 3 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7799897 No 2010-09-21 2022-06-09 US US7041786 No 2006-05-09 2023-03-25 US US9616097 No 2017-04-11 2032-07-02 US US8637451 No 2014-01-28 2022-03-28 US US9610321 No 2017-04-04 2031-09-11 US US9919024 No 2018-03-20 2031-09-15 US US9925231 No 2018-03-27 2031-09-15 US US10011637 No 2018-07-03 2034-06-05 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.25 mg/mL ALOGPS logP -1.4 ALOGPS logP 3.71 ChemAxon logS -3.8 ALOGPS pKa (Strongest Acidic) 2.43 ChemAxon Physiological Charge -8 ChemAxon Hydrogen Acceptor Count 44 ChemAxon Hydrogen Donor Count 25 ChemAxon Polar Surface Area 772.46 Å2 ChemAxon Rotatable Bond Count 28 ChemAxon Refractivity 427.55 m3·mol-1 ChemAxon Polarizability 164.58 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Heme binding
- Specific Function
- Has guanylyl cyclase on binding to the beta-1 subunit.Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.
- Gene Name
- GUCY1A2
- Uniprot ID
- P33402
- Uniprot Name
- Guanylate cyclase soluble subunit alpha-2
- Molecular Weight
- 81749.185 Da
Drug created on February 27, 2017 21:46 / Updated on February 21, 2021 18:54