linaclotide 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
peptides and glycopeptides 4622 851199-59-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • linzess
  • linaclotide
  • constella
  • MD-1100
  • MD-1100 acetate
  • linaclotide acetate
Linaclotide is a guanylate cyclase-C (GC-C) agonist. Both linaclotide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevation in intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit. In animal models, linaclotide has been shown to both accelerate GI transit and reduce intestinal pain. The linaclotide-induced reduction in visceral pain in animals is thought to be mediated by increased extracellular cGMP, which was shown to decrease the activity of pain-sensing nerves.
  • Molecular weight: 1526.73
  • Formula: C59H79N15O21S6
  • CLOGP: -2.58
  • LIPINSKI: 3
  • HAC: 36
  • HDO: 19
  • TPSA: 573.91
  • ALOGS: -3.34
  • ROTB: 13

Drug dosage:

DoseUnitRoute
0.29 mg O

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Aug. 30, 2012 FDA FOREST LABS LLC
Dec. 19, 2016 PMDA ASTELLAS PHARMA INC.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 135.33 15.02 358 11184 638149 55642376
Constipation 102.41 15.02 163 11379 201780 56078745
Product dose omission issue 80.95 15.02 148 11394 204605 56075920
Abdominal distension 62.05 15.02 78 11464 77548 56202977
Abdominal pain 38.91 15.02 129 11413 258676 56021849
Rheumatoid arthritis 38.81 15.02 15 11527 382589 55897936
Inappropriate schedule of product administration 37.67 15.02 64 11478 83323 56197202
Headache 35.30 15.02 215 11327 558829 55721696
Incorrect dose administered 34.55 15.02 48 11494 52499 56228026
Off label use 33.28 15.02 211 11331 555969 55724556
Migraine 33.27 15.02 62 11480 86735 56193790
Anal incontinence 30.38 15.02 23 11519 12275 56268250
Product dispensing error 26.67 15.02 19 11523 9245 56271280
Pre-existing condition improved 25.61 15.02 17 11525 7381 56273144
Product physical issue 24.77 15.02 14 11528 4568 56275957
Flatulence 24.28 15.02 31 11511 31257 56249268
Feeling abnormal 23.15 15.02 70 11472 133532 56146993
General physical health deterioration 22.24 15.02 4 11538 170006 56110519
Systemic lupus erythematosus 21.97 15.02 5 11537 180073 56100452
Illness 21.90 15.02 31 11511 34480 56246045
Maternal exposure during pregnancy 21.70 15.02 6 11536 189547 56090978
Glossodynia 21.26 15.02 3 11539 152455 56128070
Surgery 20.34 15.02 29 11513 32457 56248068
Treatment failure 20.26 15.02 5 11537 170387 56110138
Anxiety 18.84 15.02 84 11458 193088 56087437
Intentional product misuse 18.74 15.02 36 11506 51468 56229057
Muscle spasms 18.43 15.02 66 11476 137305 56143220
Intervertebral disc compression 18.05 15.02 7 11535 974 56279551
Malaise 17.44 15.02 132 11410 367728 55912797
Arthropathy 16.98 15.02 10 11532 200265 56080260
Product storage error 16.94 15.02 17 11525 13196 56267329
Wound 16.64 15.02 4 11538 138800 56141725
Product packaging quantity issue 16.61 15.02 7 11535 1207 56279318
Drug intolerance 16.48 15.02 18 11524 264800 56015725
Therapy interrupted 16.23 15.02 23 11519 25602 56254923
Contraindicated product administered 16.22 15.02 9 11533 186277 56094248
Subacute hepatic failure 16.20 15.02 4 11538 122 56280403
Thrombocytopenia 16.18 15.02 4 11538 136220 56144305
Lymph node pain 15.97 15.02 7 11535 1328 56279197
Impaired gastric emptying 15.87 15.02 14 11528 9249 56271276
Multiple sclerosis relapse 15.86 15.02 31 11511 44872 56235653
Gastrointestinal infection 15.71 15.02 13 11529 7881 56272644
Infusion related reaction 15.61 15.02 12 11530 208919 56071606
Nausea 15.60 15.02 231 11311 763947 55516578
Completed suicide 15.22 15.02 61 11481 133772 56146753

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 99.48 23.73 123 2141 352286 31342794
Constipation 51.12 23.73 53 2211 123938 31571142
Prescribed underdose 44.14 23.73 18 2246 8260 31686820
Off label use 41.59 23.73 82 2182 347192 31347888
Drug ineffective 34.28 23.73 82 2182 395491 31299589
Inappropriate schedule of product administration 30.93 23.73 27 2237 50796 31644284
Incorrect dose administered 25.88 23.73 21 2243 35731 31659349
Urinary retention 24.81 23.73 20 2244 33705 31661375

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Constipation 100.61 16.36 149 9849 252289 70666157
Diarrhoea 86.80 16.36 274 9724 783067 70135379
Product dose omission issue 66.74 16.36 114 9884 217354 70701092
Headache 45.84 16.36 182 9816 580223 70338223
Incorrect dose administered 41.36 16.36 49 9949 66670 70851776
Abdominal distension 37.63 16.36 59 9939 104610 70813836
Inappropriate schedule of product administration 29.83 16.36 54 9944 107501 70810945
Abdominal pain 26.67 16.36 107 9891 342020 70576426
Off label use 26.47 16.36 187 9811 742873 70175573
Malaise 23.73 16.36 122 9876 432810 70485636
Nausea 23.46 16.36 202 9796 851886 70066560
Dizziness 22.85 16.36 127 9871 464014 70454432
Acute kidney injury 20.54 16.36 22 9976 474602 70443844
Anxiety 20.53 16.36 73 9925 220257 70698189
Flatulence 20.35 16.36 26 9972 38155 70880291
Intervertebral disc compression 20.13 16.36 7 9991 1046 70917400
Feeling abnormal 19.59 16.36 54 9944 142265 70776181
Multiple sclerosis relapse 19.41 16.36 27 9971 42990 70875456
Migraine 18.43 16.36 35 9963 72203 70846243
Lymph node pain 17.98 16.36 7 9991 1436 70917010
Anal incontinence 17.20 16.36 16 9982 16474 70901972
Oesophageal hypomotility 17.16 16.36 4 9994 140 70918306
Rheumatoid arthritis 17.04 16.36 10 9988 291795 70626651

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A06AX04 ALIMENTARY TRACT AND METABOLISM
DRUGS FOR CONSTIPATION
DRUGS FOR CONSTIPATION
Other drugs for constipation
MeSH PA D020536 Enzyme Activators
MeSH PA D005765 Gastrointestinal Agents
MeSH PA D000074268 Guanylyl Cyclase C Agonists
FDA MoA N0000185499 Guanylate Cyclase Activators
FDA EPC N0000185500 Guanylate Cyclase-C Agonist
CHEBI has role CHEBI:68553 GC-C agonists

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Irritable bowel syndrome indication 10743008 DOID:9778
Chronic idiopathic constipation indication 82934008
Irritable bowel syndrome characterized by constipation indication 440630006




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.46 acidic
pKa2 4.13 acidic
pKa3 9.65 acidic
pKa4 10.31 acidic
pKa5 12.22 acidic
pKa6 12.57 acidic
pKa7 12.94 acidic
pKa8 13.17 acidic
pKa9 13.37 acidic
pKa10 13.69 acidic
pKa11 13.86 acidic
pKa12 13.98 acidic
pKa13 6.73 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8110553 Jan. 28, 2024 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8110553 Jan. 28, 2024 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 8110553 Jan. 28, 2024 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 7304036 Aug. 30, 2026 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 8933030 Feb. 17, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 10702576 Aug. 11, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 8748573 Oct. 30, 2031 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
290MCG LINZESS ALLERGAN N202811 Aug. 30, 2012 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
72MCG LINZESS ALLERGAN N202811 Jan. 25, 2017 RX CAPSULE ORAL 9708371 Aug. 16, 2033 METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Heat-stable enterotoxin receptor Enzyme AGONIST Ki 8.91 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Heat-stable enterotoxin receptor Enzyme AGONIST Ki 8.38 IUPHAR

External reference:

IDSource
D06612 KEGG_DRUG
4031965 VANDF
CHEBI:68551 CHEBI
CHEMBL3301675 ChEMBL_ID
C523483 MESH_SUPPLEMENTAL_RECORD_UI
5017 IUPHAR_LIGAND_ID
8802 INN_ID
851199-60-5 SECONDARY_CAS_RN
DB08890 DRUGBANK_ID
N0TXR0XR5X UNII
1307404 RXNORM
192786 MMSL
28804 MMSL
d07902 MMSL
014633 NDDF
703126002 SNOMEDCT_US
703686003 SNOMEDCT_US
C2000261 UMLSCUI
CHEMBL3301676 ChEMBL_ID
16158208 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Linzess HUMAN PRESCRIPTION DRUG LABEL 1 0456-1201 CAPSULE, GELATIN COATED 145 ug ORAL NDA 29 sections
Linzess HUMAN PRESCRIPTION DRUG LABEL 1 0456-1202 CAPSULE, GELATIN COATED 290 ug ORAL NDA 29 sections
Linzess HUMAN PRESCRIPTION DRUG LABEL 1 0456-1203 CAPSULE, GELATIN COATED 72 ug ORAL NDA 29 sections