Camostat (100 μg/kg i.t.) induces a potent and prolonged attenuation of ENaC activity in the guinea pig trachea. Camostat mesilate (1-2 mg/g of diet) markedly attenuats an increase in hepatic plasmin and TGF-beta levels, HSC activation, and hepatic fibrosis without apparent systemic or local side effects in porcine serum–treated rats. Camostat mesilate (1 mg/g) prevents pancreatic atrophy and improves pancreatic exocrine function of rat chronic pancreatitis induced by DBTC. Camostat mesilate (1 mg/g) inhibits chronic inflammation and pancreatic fibrosis induced by DBTC. Camostat mesilate (1 mg/g) inhibits the development of pancreatic fibrosis and PSCs activation in the pancreas induced by DBTC. Camostat mesilate (1 mg/g) suppresses monocytes infiltration and inhibits MCP-1 expression both in serum and in pancreatic tissue. Camostat mesilate (100 mg/kg) significantly increases the body weight and pancreatic wet weight, and it significantly inhibits inflammatory changes and fibrosis of the pancreas through the suppression of gene expressions of PAP, p8, and cytokines in rat chronic pancreatitis.

Absorption, Distribution and Excretion
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.
Camostat mesylate is 89.8-95.6% eliminated in the urine and 1.0-1.7% eliminated in the feces.
The volume of distribution at steady state of camostat mesylate is 0.34-1.31L/kg.
The clearance of camostat mesylate is 4.5-7.3mL/min/kg.

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Metabolism / Metabolites
Camostat mesylate is hydrolyzed by carboxyesterate to the active 4-(4-guanidinobenzoyloxy) phenylacetate. The active metabolite is further hydrolyzed by arylesterase to 4-guanidinobenzoic acid.

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Biological Half-Life
The half life of camostat mesylate is 3.8-4.7h.

Protein Binding
Camostat mesylate is 25.8-28.2% protein bound to human serum proteins _in vitro_.

Camostat is a benzoate ester resulting from the formal condensation of the carboxy group of 4-guanidinobenzoic acid with the hydroxy group of 2-(dimethylamino)-2-oxoethyl (4-hydroxyphenyl)acetate. It is a potent inhibitor of the human transmembrane protease serine 2 (TMPRSS2) and its mesylate salt is currently under investigation for its effectiveness in COVID-19 patients. It has a role as an anticoronaviral agent, a serine protease inhibitor, an antifibrinolytic drug, an anti-inflammatory agent, an antiviral agent, an antihypertensive agent and an antineoplastic agent. It is a tertiary carboxamide, a carboxylic ester, a diester, a member of guanidines and a benzoate ester. It is functionally related to a 4-guanidinobenzoic acid. It is a conjugate base of a camostat(1+).
Camostat mesylate, or FOY-305, is a synthetic serine protease inhibitor. It was first described in the literature in 1981, as part of research on the inhibition of skin tumors in mice. Camostat mesylate inhibits cholecystokinin, pro-inflammatory cytokines, and serine proteases, leading to it being investigated for multiple indications including the treatment of COVID-19. Camostat mesylate was first approved in Japan in January 2006.
Camostat is an orally bioavailable, synthetic serine protease inhibitor, with anti-inflammatory, antifibrotic, and potential antiviral activities. Upon oral administration, camostat and its metabolite 4-(4-guanidinobenzoyloxyl)phenyl acetic acid (FOY 251) inhibit the activities of a variety of proteases, including trypsin, kallikrein, thrombin and plasmin, and C1r- and C1 esterases. Although the mechanism of action of camostat is not fully understood, trypsinogen activation in the pancreas is known to be a trigger reaction in the development of pancreatitis. Camostat blocks the activation of trypsinogen to trypsin and the inflammatory cascade that follows. Camostat may also suppress the expression of the cytokines interleukin-1beta (IL-1b), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and transforming growth factor-beta (TGF-beta), along with alpha-smooth muscle actin (alpha-SMA). This reduces inflammation and fibrosis of the pancreas. In addition, camostat may inhibit the activity of transmembrane protease, serine 2 (TMPRSS2), a host cell serine protease that mediates viral cell entry for influenza virus and coronavirus, thereby inhibiting viral infection and replication.

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Drug Indication
Camostat mesylate is indicated in Japan to treat chronic pancreatitis and drug induced lung injury. It is also being investigated as a potential treatment for COVID-19.

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Mechanism of Action
In rats, oral camostat mesylate may increase pancreatic secretions and hypertrophy by increasing cholecystokinin release. Administration in rats has also lead to lower levels of IL-1beta, IL-6, TNF-alpha, TGF-beta, and PSC. 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. 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.

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

C21H26N4O8S

494.519

398.159

59721-28-7

59721-29-8 (mesylate);59721-28-7;

2536

Typically exists as solid at room temperature

1.3±0.1 g/cm3

634.6±65.0 °C at 760 mmHg

194-198ºC

337.6±34.3 °C

0.0±1.9 mmHg at 25°C

1.597

1.29

2

6

9

29

602

0

O=C(OC1=CC=C(CC(OCC(N(C)C)=O)=O)C=C1)C2=CC=C(NC(N)=N)C=C2

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)

[4-[2-[2-(dimethylamino)-2-oxoethoxy]-2-oxoethyl]phenyl] 4-(diaminomethylideneamino)benzoate

FOY 305 Synonym

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)