CAMOSTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H22N4O5
Molecular Weight	398.4125
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=XASIMHXSUQUHLV-UHFFFAOYSA-N

InChI=1S/C20H22N4O5/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/h3-10H,11-12H2,1-2H3,(H4,21,22,23)

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 8297	1.0 nM [Ki]
Matriptase 2 Target ID: CHEMBL3018 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19190233	Inhibitor 8297	4.0 nM [Ki]
Prostasin 2 Target ID: CHEMBL5610 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19190233	Inhibitor 8297	0.576 µM [Ki]
Amiloride-sensitive sodium channel, ENaC 4 Target ID: CHEMBL2107836 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19190233	Inhibitor 8297	50.0 nM [IC50]
Plasma kallikrein 6 Target ID: CHEMBL2000 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3040018	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Multiple sclerosis 104 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 8429	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 8429	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 567 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22038264	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
New orally active serine protease inhibitors.	1995 Jul 7	7629790
Acceleration of ulcer healing by cholecystokinin (CCK): role of CCK-A receptors, somatostatin, nitric oxide and sensory nerves.	1999 Jun 30	10458643
Preparation and characterization of biodegradable or enteric-coated microspheres containing the protease inhibitor camostat.	2001 Feb	11273024
Different effects of oral administration of synthetic trypsin inhibitor on the pancreas between cholecystokinin-A receptor gene knockout mice and wild type mice.	2002 Jul	12184735
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
CCK-58 is the only detectable endocrine form of cholecystokinin in rat.	2003 Aug	12686511
Circulating ethanol does not stimulate pancreatic secretion in conscious rats.	2003 Nov	14576503
Differential mechanism and site of action of CCK on the pancreatic secretion and growth in rats.	2003 Oct	12801885
Calcineurin mediates pancreatic growth in protease inhibitor-treated mice.	2004 May	14684381
Preventive and therapeutic effects of the protease inhibitor camostat on pancreatic fibrosis and atrophy in CCK-1 receptor-deficient rats.	2005 Jan	15632700
Camostat, an oral trypsin inhibitor, reduces pancreatic fibrosis induced by repeated administration of a superoxide dismutase inhibitor in rats.	2005 Jun	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 May	15877292
Calcineurin-dependent and calcineurin-independent signal transduction pathways activated as part of pancreatic growth.	2006 Apr	16628088
[Effects of Chinese herbal medicines on spontaneous chronic pancreatitis in rats and the pathological relationships between formulas and syndromes].	2006 Jul	16834971
Activation of the mTOR signalling pathway is required for pancreatic growth in protease-inhibitor-fed mice.	2006 Jun 15	16613881
Effects of the cholecystokinin A receptor antagonist loxiglumide on the proliferation and cell cycle time of pancreatic acinar cells in rats.	2006 Mar	16552340
Strategies of development of antiviral agents directed against influenza virus replication.	2007	18220789
Pancreatic diabetes in a follow-up survey of chronic pancreatitis in Japan.	2007 Apr	17464458
[Fibrosis markers in heavy alcohol drinkers].	2007 Aug	17882797
Induction of early response genes in trypsin inhibitor-induced pancreatic growth.	2007 Feb	17095753
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 Mar	17082351
Matrix metalloproteinase gene delivery for liver fibrosis.	2008 Feb	17577645
CCK-induced pancreatic growth is not limited by mitogenic capacity in mice.	2008 May	18356533
Activation of submucosal but not myenteric plexus of the gastrointestinal tract accompanies reduction of food intake by camostat.	2008 Oct 9	18620003
Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations.	2009 May	19388054
Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease.	2009 May	19190233
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 Feb	20023007
Reduced sodium transport with nasal administration of the prostasin inhibitor camostat in subjects with cystic fibrosis.	2013 Jul	23412700

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

Official Name

English

camostat [INN]

Common Name

English

CAMOSTAT [MI]

Common Name

English

Camostat [WHO-DD]

Common Name

English

P-GUANIDINOBENZOIC ACID, ESTER WITH (P-HYDROXYPHENYL)ACETIC ACID, ESTER WITH N,N-DIMETHYLGLYCOLAMIDE

Common Name

English

Classification Tree Code System Code

WHO-VATC

QB02AB04