CAMOSTAT MESYLATE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H22N4O5.CH4O3S
Molecular Weight	494.518
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CS(O)(=O)=O.CN(C)C(=O)COC(=O)CC1=CC=C(OC(=O)C2=CC=C(NC(N)=N)C=C2)C=C1

InChI

InChIKey=FSEKIHNIDBATFG-UHFFFAOYSA-N

InChI=1S/C20H22N4O5.CH4O3S/c1-24(2)17(25)12-28-18(26)11-13-3-9-16(10-4-13)29-19(27)14-5-7-15(8-6-14)23-20(21)22;1-5(2,3)4/h3-10H,11-12H2,1-2H3,(H4,21,22,23);1H3,(H,2,3,4)

HIDE SMILES / InChI

Description
Sources: http://www.e-search.ne.jp/~jpr/PDF/ONO01.PDF
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19190233 | https://www.ncbi.nlm.nih.gov/pubmed/3040018

Camostat mesilate (FOY-305) is a synthetic f low-molecular weight protease inhibitor. It is able to inhibit trypsin, prostasin, matriptase and plasma kallikrein. In addition camostat attenuates airway epithelial sodium channel function and enhances mucociliary clearance. Camostat mesilate tablets (FOIPAN®) are approved in Japan and used for the treatment of remission of acute symptoms of chronic pancreatitis and postoperative reflux esophagitis.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Potency
Trypsin 7 Target ID: CHEMBL2095204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19190233	Inhibitor 8504	1.0 nM [Ki]
Matriptase 2 Target ID: CHEMBL3018 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19190233	Inhibitor 8504	4.0 nM [Ki]
Prostasin 2 Target ID: CHEMBL5610 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19190233	Inhibitor 8504	0.576 µM [Ki]
Amiloride-sensitive sodium channel, ENaC 4 Target ID: CHEMBL2107836 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19190233	Inhibitor 8504	50.0 nM [IC50]
Plasma kallikrein 9 Target ID: CHEMBL2000 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3040018	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Multiple sclerosis 107 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2455235	Primary	Preclinical	Unknown Approved Use Unknown
Chronic pancreatitis 3 Sources: http://www.e-search.ne.jp/~jpr/PDF/ONO01.PDF https://www.ncbi.nlm.nih.gov/pubmed/2909420 https://www.ncbi.nlm.nih.gov/pubmed/17625311	Primary	Approved 8583	FOIPAN Approved Use INDICATIONS 1. Remission of acute symptoms of chronic pancreatitis 2. Postoperative reflux esophagitis Launch Date 1994
Postoperative reflux esophagitis 2 Sources: http://www.e-search.ne.jp/~jpr/PDF/ONO01.PDF	Primary	Approved 8583	FOIPAN Approved Use INDICATIONS 1. Remission of acute symptoms of chronic pancreatitis 2. Postoperative reflux esophagitis Launch Date 1994
Hepatic fibrosis 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11375959	Primary	Preclinical	Unknown Approved Use Unknown
Hypertension 575 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22038264	Primary	Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
371 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
95.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
93.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
177 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
218 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
367 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
87.1 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/180188_3999003F1297_1_007_3F.pdf#page=31	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
683 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
206 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
194 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
227 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
366 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
556 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
10400 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/180188_3999003F1297_1_007_3F.pdf#page=31	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.58 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.33 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1.16 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1.35 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.05 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.962 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33982445/	600 mg 4 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
100 min OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/180188_3999003F1297_1_007_3F.pdf#page=31	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	4-(4-GUANIDINOBENZOYLOXY)PHENYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
71.8% OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/180188_3999003F1297_1_007_3F.pdf#page=33			CAMOSTAT serum	Homo sapiens

Doses

Dose	Population	Adverse events
800 mg 4 times / day multiple, oral Highest studied dose Dose: 800 mg, 4 times / day Route: oral Route: multiple Dose: 800 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33982445/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/33982445/	Sources: https://pubmed.ncbi.nlm.nih.gov/33982445/

PubMed

Title	Date	PubMed
Reduced sodium transport with nasal administration of the prostasin inhibitor camostat in subjects with cystic fibrosis.	2013-07	23412700
ONO 3403, a synthetic serine protease inhibitor, inhibits lipopolysaccharide-induced tumor necrosis factor-{alpha} and nitric oxide production and protects mice from lethal endotoxic shock.	2011-02	20023007
Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations.	2009-05	19388054
Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease.	2009-05	19190233
Activation of submucosal but not myenteric plexus of the gastrointestinal tract accompanies reduction of food intake by camostat.	2008-10-09	18620003
CCK-induced pancreatic growth is not limited by mitogenic capacity in mice.	2008-05	18356533
Matrix metalloproteinase gene delivery for liver fibrosis.	2008-02	17577645
[Fibrosis markers in heavy alcohol drinkers].	2007-08	17882797
Pancreatic diabetes in a follow-up survey of chronic pancreatitis in Japan.	2007-04	17464458
Endogenous cholecystokinin reduces food intake and increases Fos-like immunoreactivity in the dorsal vagal complex but not in the myenteric plexus by CCK1 receptor in the adult rat.	2007-03	17082351
Induction of early response genes in trypsin inhibitor-induced pancreatic growth.	2007-02	17095753
Strategies of development of antiviral agents directed against influenza virus replication.	2007	18220789
[Effects of Chinese herbal medicines on spontaneous chronic pancreatitis in rats and the pathological relationships between formulas and syndromes].	2006-07	16834971
Activation of the mTOR signalling pathway is required for pancreatic growth in protease-inhibitor-fed mice.	2006-06-15	16613881
Calcineurin-dependent and calcineurin-independent signal transduction pathways activated as part of pancreatic growth.	2006-04	16628088
Effects of the cholecystokinin A receptor antagonist loxiglumide on the proliferation and cell cycle time of pancreatic acinar cells in rats.	2006-03	16552340
Camostat, an oral trypsin inhibitor, reduces pancreatic fibrosis induced by repeated administration of a superoxide dismutase inhibitor in rats.	2005-06	15946137
Synthetic protease inhibitor camostat prevents and reverses dyslipidemia, insulin secretory defects, and histological abnormalities of the pancreas in genetically obese and diabetic rats.	2005-05	15877292
Preventive and therapeutic effects of the protease inhibitor camostat on pancreatic fibrosis and atrophy in CCK-1 receptor-deficient rats.	2005-01	15632700
Calcineurin mediates pancreatic growth in protease inhibitor-treated mice.	2004-05	14684381
Circulating ethanol does not stimulate pancreatic secretion in conscious rats.	2003-11	14576503
Differential mechanism and site of action of CCK on the pancreatic secretion and growth in rats.	2003-10	12801885
CCK-58 is the only detectable endocrine form of cholecystokinin in rat.	2003-08	12686511
Estimation of bioavailability of salmon calcitonin from the hypocalcemic effect in rats (II): effect of protease inhibitor on the pharmacokinetic-pharmacodynamic relationship after intranasal administration.	2003	15618756
Different effects of oral administration of synthetic trypsin inhibitor on the pancreas between cholecystokinin-A receptor gene knockout mice and wild type mice.	2002-07	12184735
Preparation and characterization of biodegradable or enteric-coated microspheres containing the protease inhibitor camostat.	2001-02	11273024
Acceleration of ulcer healing by cholecystokinin (CCK): role of CCK-A receptors, somatostatin, nitric oxide and sensory nerves.	1999-06-30	10458643
New orally active serine protease inhibitors.	1995-07-07	7629790

Patents

Sample Use Guides

In Vivo Use Guide

1. Remission of acute symptoms of chronic pancreatitis. The usual dosage for oral use is 600 mg of camostat mesilate daily in three divided doses. The dosage may be adjusted according to the patient’s symptoms. 2. Postoperative reflux esophagitis. The usual dosage for oral use is 300 mg of camostat mesilate daily in three divided doses after each meal.

Route of Administration: Oral

In Vitro Use Guide

Camostat mesilate (500 uM) inhibited generation of TGF-beta by suppressing plasmin activity and reduced the activity of TGF-beta, which blocked in vitro activation of the rat hepatic stellate cells.

Name

Type

Language

CAMOSTAT MESYLATE

Common Name

English

CAMOSTAT MESILATE

Preferred Name

English

CAMOSTAT METHANESULFONATE [MI]

Common Name

English

CAMOSTAT MESILATE [MART.]

Common Name

English

CAMOSTAT MESILATE [JAN]

Common Name

English

Camostat mesilate [WHO-DD]

Common Name

English

CAMOSTAT METHANESULFONATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C783