NAV

Camostat

Identification

Summary

Camostat is a serine protease indicated in Japan to treat chronic pancreatitis.

Generic Name
Camostat
DrugBank Accession Number
DB13729
Background

Camostat mesylate, or FOY-305, is a synthetic serine protease inhibitor.2,4 It was first described in the literature in 1981, as part of research on the inhibition of skin tumors in mice.8 Camostat mesylate inhibits cholecystokinin, pro-inflammatory cytokines, and serine proteases, leading to it being investigated for multiple indications including the treatment of COVID-19.6,7,1

Camostat mesylate was first approved in Japan in January 2006.9

Type
Small Molecule
Groups
Experimental
Structure
3D
Similar Structures
Weight
Average: 398.4125
Monoisotopic: 398.159019834
Chemical Formula
C20H22N4O5
Synonyms
  • Camostat
  • Camostatum
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Pharmacology

Indication

Camostat mesylate is indicated in Japan to treat chronic pancreatitis and drug induced lung injury.3 It is also being investigated as a potential treatment for COVID-19.1

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Camostat mesylate is a protease inhibitor used to treat chronic pancreatitis.3 The duration of action is not long, as it is typically given in 3 divided doses daily.9 Patients should be counselled regarding the risk of anaphylaxis, thrombocytopenia, hepatic dysfunction, and hyperkalemia.9

Mechanism of action

In rats, oral camostat mesylate may increase pancreatic secretions and hypertrophy by increasing cholecystokinin release.6 Administration in rats has also lead to lower levels of IL-1beta, IL-6, TNF-alpha, TGF-beta, and PSC.7 Similar activity is seem after administration in humans, leading to reduced pain and inflammation as well as improve the function of the pancrease in chronic pancreatitis.9

In the case of SARS-CoV-2, camostat mesylate inhibits the action of the serine protease TMPRSS2, preventing the priming of the viral spike protein for attachment to ACE2, and entry into the cell.1

TargetActionsOrganism
UTrypsin-1
inhibitor
Humans
UTransmembrane protease serine 2
inhibitor
Humans
USuppressor of tumorigenicity 14 protein
inhibitor
Humans
UCholecystokinin
inhibitor
Humans
Absorption

A 200mg oral dose of camostat mesylate leads to the active metabolite reaching a Cmax of 87.1 ± 29.5 ng/mL, with a Tmax of 40 min, and an AUC of 10,400 ± 1,400 ng*min/mL.9

Volume of distribution

The volume of distribution at steady state of camostat mesylate is 0.34-1.31L/kg.2

Protein binding

Camostat mesylate is 25.8-28.2% protein bound to human serum proteins in vitro.9

Metabolism

Camostat mesylate is hydrolyzed by carboxyesterate to the active 4-(4-guanidinobenzoyloxy) phenylacetate.2,9 The active metabolite is further hydrolyzed by arylesterase to 4-guanidinobenzoic acid.2,9

Hover over products below to view reaction partners

Route of elimination

Camostat mesylate is 89.8-95.6% eliminated in the urine and 1.0-1.7% eliminated in the feces.2

Half-life

The half life of camostat mesylate is 3.8-4.7h.2

Clearance

The clearance of camostat mesylate is 4.5-7.3mL/min/kg.2

Adverse Effects
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Toxicity

Data regarding overdoses of camostat mesylate are not readily available, however common adverse effects include rash, pruritus, nausea, abnormal laboratory test values, and diarrhea.9

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
Albutrepenonacog alfaCamostat may increase the thrombogenic activities of Albutrepenonacog alfa.
Alpha-1-proteinase inhibitorAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Camostat.
AlteplaseThe therapeutic efficacy of Camostat can be decreased when used in combination with Alteplase.
Aminocaproic acidAminocaproic acid may increase the thrombogenic activities of Camostat.
Andexanet alfaCamostat may increase the thrombogenic activities of Andexanet alfa.
Food Interactions
  • Take with food. Take after a meal.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Camostat mesilate451M50A1EQ59721-29-8FSEKIHNIDBATFG-UHFFFAOYSA-N

Categories

ATC Codes
B02AB04 — Camostat
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as depsides and depsidones. These are polycyclic compounds that is either a polyphenolic compound composed of two or more monocyclic aromatic units linked by an ester bond (depside), or a compound containing the depsidone structure (depsidone).
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Depsides and depsidones
Sub Class
Not Available
Direct Parent
Depsides and depsidones
Alternative Parents
Guanidinobenzoic acids and derivatives / Phenol esters / Benzoic acid esters / Phenoxy compounds / Benzoyl derivatives / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Guanidines / Carboxylic acid esters / Propargyl-type 1,3-dipolar organic compounds
show 4 more
Substituents
Aromatic homomonocyclic compound / Benzenoid / Benzoate ester / Benzoic acid or derivatives / Benzoyl / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Carboxylic acid ester / Depside backbone
show 16 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans

Chemical Identifiers

UNII
0FD207WKDU
CAS number
59721-28-7
InChI Key
XASIMHXSUQUHLV-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-{2-[(dimethylcarbamoyl)methoxy]-2-oxoethyl}phenyl 4-carbamimidamidobenzoate
SMILES
CN(C)C(=O)COC(=O)CC1=CC=C(OC(=O)C2=CC=C(NC(N)=N)C=C2)C=C1

References

General References
  1. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S: SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5. [Article]
  2. Midgley I, Hood AJ, Proctor P, Chasseaud LF, Irons SR, Cheng KN, Brindley CJ, Bonn R: Metabolic fate of 14C-camostat mesylate in man, rat and dog after intravenous administration. Xenobiotica. 1994 Jan;24(1):79-92. doi: 10.3109/00498259409043223. [Article]
  3. Ota S, Hara Y, Kanoh S, Shinoda M, Kawano S, Fujikura Y, Kawana A, Shinkai M: Acute eosinophilic pneumonia caused by camostat mesilate: The first case report. Respir Med Case Rep. 2016 Jun 16;19:21-3. doi: 10.1016/j.rmcr.2016.06.005. eCollection 2016. [Article]
  4. Kitamura K, Tomita K: Proteolytic activation of the epithelial sodium channel and therapeutic application of a serine protease inhibitor for the treatment of salt-sensitive hypertension. Clin Exp Nephrol. 2012 Feb;16(1):44-8. doi: 10.1007/s10157-011-0506-1. Epub 2011 Nov 1. [Article]
  5. Tamura Y, Hirado M, Okamura K, Minato Y, Fujii S: Synthetic inhibitors of trypsin, plasmin, kallikrein, thrombin, C1r-, and C1 esterase. Biochim Biophys Acta. 1977 Oct 13;484(2):417-22. [Article]
  6. Goke B, Printz H, Koop I, Rausch U, Richter G, Arnold R, Adler G: Endogenous CCK release and pancreatic growth in rats after feeding a proteinase inhibitor (camostate). Pancreas. 1986;1(6):509-15. doi: 10.1097/00006676-198611000-00008. [Article]
  7. Jia D, Taguchi M, Otsuki M: Synthetic protease inhibitor camostat prevents and reverses dyslipidemia, insulin secretory defects, and histological abnormalities of the pancreas in genetically obese and diabetic rats. Metabolism. 2005 May;54(5):619-27. doi: 10.1016/j.metabol.2004.12.005. [Article]
  8. Ohkoshi M: Inhibition of growth of 3-methylcholanthrene-induced mouse skin tumor by protease inhibitor [N,N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate. Gan. 1981 Dec;72(6):959-64. [Article]
  9. Ono Pharmaceutical: Foipan Camostat Mesilate Oral Tablets [Link]
ChemSpider
2440
BindingDB
50424712
ChEBI
135632
ChEMBL
CHEMBL590799
ZINC
ZINC000003871842
Wikipedia
Camostat

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4WithdrawnTreatmentCoronavirus Disease 2019 (COVID‑19) / COVID1
3CompletedTreatmentCoronavirus Disease 2019 (COVID‑19)1
3TerminatedTreatmentCoronavirus Disease 2019 (COVID‑19)1
3TerminatedTreatmentCoronavirus Disease 2019 (COVID‑19) / Seasonal Allergic Rhinitis1
3Unknown StatusTreatmentCoronavirus Disease 2019 (COVID‑19)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)194-198Pharmaceutical and Medical Devices Agency Japan
Predicted Properties
PropertyValueSource
Water Solubility0.0626 mg/mLALOGPS
logP1.88ALOGPS
logP1.51Chemaxon
logS-3.8ALOGPS
pKa (Strongest Acidic)19.54Chemaxon
pKa (Strongest Basic)8.54Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area134.81 Å2Chemaxon
Rotatable Bond Count9Chemaxon
Refractivity117.77 m3·mol-1Chemaxon
Polarizability41.92 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0900000000-082530f6703612ed3bd1
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0uki-9521000000-d5934cd9fe5aeda04647
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-5950000000-64cc0c66c73f58462655
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-022c-3194000000-0e6b07ec56d42a5940ad
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-006t-4901000000-fddab89c0d8af7bdbe41
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0fdp-3190000000-090e7ca074e860038e12
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-191.08212
predicted
DeepCCS 1.0 (2019)
[M+H]+193.44012
predicted
DeepCCS 1.0 (2019)
[M+Na]+200.1066
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Details1. Trypsin-1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine-type endopeptidase activity
Specific Function
Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form aga...
Gene Name
PRSS1
Uniprot ID
P07477
Uniprot Name
Trypsin-1
Molecular Weight
26557.88 Da
References
  1. Senokuchi K, Nakai H, Nakayama Y, Odagaki Y, Sakaki K, Kato M, Maruyama T, Miyazaki T, Ito H, Kamiyasu K, et al.: New orally active serine protease inhibitors. J Med Chem. 1995 Jul 7;38(14):2521-3. doi: 10.1021/jm00014a003. [Article]
  2. Tamura Y, Hirado M, Okamura K, Minato Y, Fujii S: Synthetic inhibitors of trypsin, plasmin, kallikrein, thrombin, C1r-, and C1 esterase. Biochim Biophys Acta. 1977 Oct 13;484(2):417-22. [Article]
Details2. Transmembrane protease serine 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:26018085, PubMed:25122198). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity).
Specific Function
Scavenger receptor activity
Gene Name
TMPRSS2
Uniprot ID
O15393
Uniprot Name
Transmembrane protease serine 2
Molecular Weight
53858.845 Da
References
  1. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S: SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5. [Article]
Details3. Suppressor of tumorigenicity 14 protein
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine-type peptidase activity
Specific Function
Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the...
Gene Name
ST14
Uniprot ID
Q9Y5Y6
Uniprot Name
Suppressor of tumorigenicity 14 protein
Molecular Weight
94769.01 Da
References
  1. Kitamura K, Tomita K: Proteolytic activation of the epithelial sodium channel and therapeutic application of a serine protease inhibitor for the treatment of salt-sensitive hypertension. Clin Exp Nephrol. 2012 Feb;16(1):44-8. doi: 10.1007/s10157-011-0506-1. Epub 2011 Nov 1. [Article]
Details4. Cholecystokinin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear. Binding to CCK-A receptors stimulates amylase release from the pancreas, binding to CCK-B receptors stimulates gastric acid secretion.
Specific Function
Hormone activity
Gene Name
CCK
Uniprot ID
P06307
Uniprot Name
Cholecystokinin
Molecular Weight
12669.26 Da
References
  1. Goke B, Printz H, Koop I, Rausch U, Richter G, Arnold R, Adler G: Endogenous CCK release and pancreatic growth in rats after feeding a proteinase inhibitor (camostate). Pancreas. 1986;1(6):509-15. doi: 10.1097/00006676-198611000-00008. [Article]

Drug created at June 23, 2017 20:47 / Updated at February 21, 2021 18:54