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	119.69	14.27	375	12987	714991	62760669
Product dose omission issue	86.54	14.27	167	13195	234146	63241514
Constipation	80.23	14.27	158	13204	224785	63250875
Abdominal distension	68.95	14.27	88	13274	86527	63389133
Migraine	38.46	14.27	74	13288	103272	63372388
Headache	37.30	14.27	244	13118	632997	62842663
Inappropriate schedule of product administration	36.93	14.27	73	13289	103892	63371768
Product dispensing error	35.88	14.27	24	13338	10281	63465379
Abdominal pain	34.93	14.27	138	13224	293318	63182342
Incorrect dose administered	34.31	14.27	52	13310	59916	63415744
Anal incontinence	32.10	14.27	25	13337	13551	63462109
Illness	28.71	14.27	43	13319	49016	63426644
Pre-existing condition improved	28.22	14.27	19	13343	8225	63467435
Systemic lupus erythematosus	28.16	14.27	5	13357	208913	63266747
Maternal exposure during pregnancy	28.11	14.27	6	13356	220056	63255604
Completed suicide	27.48	14.27	80	13282	145593	63330067
Off label use	27.30	14.27	238	13124	674224	62801436
General physical health deterioration	26.75	14.27	5	13357	201397	63274263
Product physical issue	25.97	14.27	15	13347	4965	63470695
Feeling abnormal	25.63	14.27	79	13283	148313	63327347
Flatulence	25.62	14.27	34	13328	34668	63440992
Glossodynia	24.72	14.27	4	13358	178872	63296788
Treatment failure	24.28	14.27	6	13356	199037	63276623
Product packaging quantity issue	22.33	14.27	9	13353	1350	63474310
Contraindicated product administered	22.21	14.27	9	13353	217639	63258021
Product storage error	22.02	14.27	21	13341	14935	63460725
Wound	21.79	14.27	4	13358	163259	63312401
Surgery	21.76	14.27	32	13330	35880	63439780
Drug intolerance	19.21	14.27	22	13340	308639	63167021
Arthropathy	19.11	14.27	13	13349	234779	63240881
Rheumatoid arthritis	18.18	14.27	16	13346	253803	63221857
Infusion related reaction	18.17	14.27	15	13347	245506	63230154
Thrombocytopenia	17.59	14.27	5	13357	151152	63324508
Malaise	17.39	14.27	148	13214	415806	63059854
Multiple sclerosis relapse	17.15	14.27	34	13328	48444	63427216
Volvulus	16.84	14.27	8	13354	1778	63473882
Anxiety	16.69	14.27	90	13272	217451	63258209
Nausea	16.68	14.27	262	13100	854209	62621451
Intervertebral disc compression	16.52	14.27	7	13355	1191	63474469
Impaired gastric emptying	16.15	14.27	15	13347	10317	63465343
Insurance issue	16.07	14.27	12	13350	6109	63469551
Muscle spasms	15.84	14.27	70	13292	156080	63319580
Subacute hepatic failure	15.73	14.27	4	13358	134	63475526
Therapy interrupted	15.60	14.27	26	13336	32429	63443231
Blood potassium decreased	15.50	14.27	30	13332	41996	63433664
Lymph node pain	15.29	14.27	7	13355	1431	63474229
Intestinal obstruction	15.18	14.27	25	13337	30874	63444786
Nervousness	15.13	14.27	25	13337	30954	63444706
COVID-19	14.90	14.27	55	13307	113048	63362612
Lower respiratory tract infection	14.28	14.27	5	13357	132302	63343358

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	97.72	22.48	132	2503	389780	34564516
Off label use	41.90	22.48	95	2540	419429	34534867
Prescribed underdose	41.88	22.48	18	2617	8915	34945381
Drug ineffective	37.61	22.48	96	2539	456655	34497641
Inappropriate schedule of product administration	32.34	22.48	31	2604	62265	34892031
Constipation	27.45	22.48	42	2593	136940	34817356
Urinary retention	24.60	22.48	21	2614	36267	34918029
Incorrect dose administered	22.61	22.48	21	2614	40494	34913802

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
Diarrhoea	77.82	14.47	291	11256	880198	78852643
Product dose omission issue	72.43	14.47	129	11418	247408	79485433
Constipation	72.16	14.47	139	11408	282911	79449930
Headache	47.81	14.47	204	11343	653568	79079273
Abdominal distension	41.05	14.47	67	11480	119583	79613258
Incorrect dose administered	37.95	14.47	51	11496	76579	79656262
Inappropriate schedule of product administration	29.63	14.47	62	11485	133566	79599275
Completed suicide	26.47	14.47	87	11460	245680	79487161
Abdominal pain	25.66	14.47	118	11429	389451	79343390
Acute kidney injury	23.91	14.47	24	11523	519380	79213461
Migraine	23.49	14.47	44	11503	87449	79645392
Malaise	22.99	14.47	135	11412	489734	79243107
Off label use	22.59	14.47	215	11332	907000	78825841
Nausea	22.45	14.47	224	11323	956972	78775869
Feeling abnormal	20.51	14.47	60	11487	159139	79573702
Flatulence	20.48	14.47	28	11519	42696	79690145
Multiple sclerosis relapse	20.09	14.47	29	11518	46504	79686337
Dizziness	19.71	14.47	137	11410	526304	79206537
Anal incontinence	19.26	14.47	18	11529	18150	79714691
General physical health deterioration	19.05	14.47	8	11539	275230	79457611
Intervertebral disc compression	18.42	14.47	7	11540	1309	79731532
Urinary tract infection	17.94	14.47	83	11464	274429	79458412
Anxiety	17.63	14.47	77	11470	248435	79484406
Neutropenia	17.43	14.47	10	11537	287700	79445141
Lymph node pain	17.31	14.47	7	11540	1543	79731298
Tooth infection	16.85	14.47	17	11530	18815	79714026
Oesophageal hypomotility	16.68	14.47	4	11543	154	79732687
Nervousness	16.17	14.47	22	11525	33393	79699448
Febrile neutropenia	15.53	14.47	7	11540	230992	79501849
Dihydrotestosterone increased	15.40	14.47	3	11544	42	79732799

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	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	8110553	Jan. 28, 2024	METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
290MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	8110553	Jan. 28, 2024	METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	8110553	Jan. 28, 2024	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	8110553	Jan. 28, 2024	TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
145MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	7304036	Aug. 30, 2026	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	7304036	Aug. 30, 2026	METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
290MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	7304036	Aug. 30, 2026	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
290MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	7304036	Aug. 30, 2026	METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULTS
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	7304036	Aug. 30, 2026	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	7304036	Aug. 30, 2026	TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	8933030	Feb. 17, 2031	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	8933030	Feb. 17, 2031	TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	10702576	Aug. 11, 2031	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	10702576	Aug. 11, 2031	TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE
145MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	8748573	Oct. 30, 2031	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	8748573	Oct. 30, 2031	METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
290MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	8748573	Oct. 30, 2031	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
290MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	8748573	Oct. 30, 2031	METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
145MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	9708371	Aug. 16, 2033	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
145MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	9708371	Aug. 16, 2033	METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
290MCG	LINZESS	ABBVIE	N202811	Aug. 30, 2012	RX	CAPSULE	ORAL	9708371	Aug. 16, 2033	METHOD OF TREATING IRRITABLE BOWEL SYNDROME WITH CONSTIPATION IN ADULT PATIENTS.
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	9708371	Aug. 16, 2033	METHOD OF TREATING CHRONIC IDIOPATHIC CONSTIPATION IN ADULT PATIENTS.
72MCG	LINZESS	ABBVIE	N202811	Jan. 25, 2017	RX	CAPSULE	ORAL	9708371	Aug. 16, 2033	TREATMENT OF FUNCTIONAL CONSTIPATION IN PEDIATRIC PATIENTS 6 TO 17 YEARS OF AGE

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