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

Stem definition	Drug id	CAS RN
peptides and glycopeptides	4622	851199-59-2

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
0.29	mg	O

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
Aug. 30, 2012	FDA	FOREST LABS LLC
Dec. 19, 2016	PMDA	ASTELLAS PHARMA INC.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (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 strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent 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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Heat-stable enterotoxin receptor	Enzyme	P25092	GUC2C_HUMAN	AGONIST	Ki	8.91		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Heat-stable enterotoxin receptor	Enzyme		GUC2C_RAT	AGONIST	Ki	8.38		IUPHAR

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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