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	136.65	14.74	347	10307	588129	50006341
Product dose omission issue	65.39	14.74	129	10525	183709	50410761
Abdominal distension	61.10	14.74	76	10578	72827	50521643
Constipation	60.90	14.74	126	10528	185582	50408888
Inappropriate schedule of product administration	37.91	14.74	60	10594	71771	50522699
Off label use	37.83	14.74	198	10456	474228	50120242
Incorrect dose administered	35.10	14.74	47	10607	48367	50546103
Headache	34.76	14.74	203	10451	506332	50088138
Abdominal pain	33.91	14.74	118	10536	236110	50358360
Migraine	29.35	14.74	55	10599	75225	50519245
Product dispensing error	26.92	14.74	19	10635	8872	50585598
Anal incontinence	26.82	14.74	21	10633	11469	50583001
Flatulence	25.11	14.74	31	10623	29427	50565043
Pre-existing condition improved	23.44	14.74	16	10638	7081	50587389
Product physical issue	22.46	14.74	13	10641	4319	50590151
Intentional product misuse	20.57	14.74	36	10618	46698	50547772
Feeling abnormal	19.11	14.74	64	10590	125428	50469042
Anxiety	18.32	14.74	80	10574	177526	50416944
Muscle spasms	18.21	14.74	63	10591	125490	50468980
Intervertebral disc compression	18.07	14.74	7	10647	946	50593524
General physical health deterioration	17.96	14.74	4	10650	142430	50452040
Maternal exposure during pregnancy	17.33	14.74	6	10648	159772	50434698
Product packaging quantity issue	17.22	14.74	7	10647	1073	50593397
Multiple sclerosis relapse	16.25	14.74	31	10623	42933	50551537
Subacute hepatic failure	16.09	14.74	4	10650	122	50594348
Lymph node pain	15.99	14.74	7	10647	1288	50593182
Product storage error	15.82	14.74	16	10638	12208	50582262
Systemic lupus erythematosus	15.74	14.74	5	10649	140617	50453853
Surgery	15.60	14.74	25	10629	30180	50564290
Malaise	15.43	14.74	122	10532	335410	50259060
Treatment failure	15.22	14.74	5	10649	137632	50456838
Glossodynia	15.07	14.74	3	10651	115566	50478904
Dysphagia	15.01	14.74	43	10611	77475	50516995

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	99.12	25.61	119	1984	332579	29239845
Prescribed underdose	45.30	25.61	18	2085	7768	29564656
Off label use	39.91	25.61	74	2029	300726	29271698
Drug ineffective	38.16	25.61	81	2022	363089	29209335
Inappropriate schedule of product administration	34.20	25.61	27	2076	44445	29527979
Incorrect dose administered	27.46	25.61	21	2082	32963	29539461
Urinary retention	25.88	25.61	20	2083	31878	29540546

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	85.07	16.22	262	9041	722442	63766987
Product dose omission issue	56.63	16.22	101	9202	194646	64294783
Constipation	53.17	16.22	108	9195	229229	64260200
Headache	45.34	16.22	173	9130	529294	63960135
Incorrect dose administered	42.47	16.22	48	9255	60717	64428712
Abdominal distension	37.61	16.22	57	9246	95937	64393492
Inappropriate schedule of product administration	33.63	16.22	53	9250	92233	64397196
Off label use	29.26	16.22	173	9130	632633	63856796
Abdominal pain	24.15	16.22	99	9204	312276	64177153
Dizziness	22.73	16.22	122	9181	430041	64059388
Anxiety	22.24	16.22	72	9231	202577	64286852
Flatulence	21.29	16.22	26	9277	35640	64453789
Nausea	20.78	16.22	188	9115	785612	63703817
Malaise	20.67	16.22	112	9191	396135	64093294
Intervertebral disc compression	20.25	16.22	7	9296	1004	64488425
Acute kidney injury	20.24	16.22	21	9282	449219	64040210
Multiple sclerosis relapse	19.87	16.22	27	9276	41108	64448321
Lymph node pain	18.26	16.22	7	9296	1345	64488084
Feeling abnormal	16.99	16.22	50	9253	133552	64355877

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
16158208	PUBCHEM_CID
1307404	RXNORM
192786	MMSL
28804	MMSL
d07902	MMSL
014633	NDDF
703126002	SNOMEDCT_US
703686003	SNOMEDCT_US
C2000261	UMLSCUI
CHEMBL3301676	ChEMBL_ID

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