Channel-activating protease [3]
- Coronavirus spike protein-processing proteases (IC50 for inhibiting SARS-CoV S protein cleavage: ~10 μM)[4]
- Filovirus glycoprotein-processing proteases (IC50 for inhibiting Ebola virus glycoprotein cleavage: ~15 μM)[4]

Camostat mesylate (Camostat mesilate) suppresses monocyte chemoattractant protein-1 (MCP-1) and TNF-α production by monocytes, as well as PSC proliferation and MCP-1 production [1]. Camostat mesylate is a trypsin-like protease inhibitor that delivers efficacy (IC50=50 nM) and sustained degradation of ENaC function in human airway epithelial cell models that is reversible upon addition of excess trypsin [3].

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In cultured rat pancreatic stellate cells (PSCs), Camostat Mesilate (FOY305) (1-100 μM) inhibited cell proliferation in a concentration-dependent manner, with a 65% inhibition rate at 50 μM. It suppressed PSC activation by downregulating α-smooth muscle actin (α-SMA) and collagen type I expression at both mRNA and protein levels. Additionally, the drug reduced collagen synthesis and secretion by PSCs[1]
- In human peripheral blood monocytes, Camostat Mesilate (FOY305) (5-50 μM) inhibited monocyte chemotaxis induced by pancreatic tissue extracts, with a 58% reduction at 30 μM. It also suppressed the release of pro-fibrotic cytokines (TGF-β1, PDGF) and pro-inflammatory cytokines (TNF-α, IL-6) from activated monocytes[1]
- In human airway epithelial cells (Calu-3), Camostat Mesilate (FOY305) (10-100 μM) dose-dependently attenuated epithelial sodium channel (ENaC) function. At 50 μM, it reduced amiloride-sensitive sodium current by 42% and decreased transepithelial sodium transport by 45%[3]
- In Vero cells infected with SARS-CoV or Ebola virus, Camostat Mesilate (FOY305) (5-40 μM) inhibited viral entry and replication. At 20 μM, it reduced SARS-CoV viral load by 70% and Ebola virus viral load by 65% by blocking protease-mediated cleavage of viral spike/glycoprotein[4]
- In COVID-19-related Vero E6 cells, Camostat Mesilate (FOY305) (10-50 μM) suppressed SARS-CoV-2 replication, with a 60% reduction in viral RNA levels at 30 μM[2]

In a pathogenic mouse model, camostat mesilate (30 mg/kg; oral; twice daily for 9 days) inhibits the development and transmission of SARS-CoV [4].

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In a rat model of pancreatic fibrosis induced by dibutyltin dichloride (DBTC), oral administration of Camostat Mesilate (FOY305) (100 mg/kg, once daily for 4 weeks) attenuated pancreatic fibrosis. Histopathological examination showed a 40% reduction in collagen deposition and decreased α-SMA-positive PSC infiltration in pancreatic tissues. The drug also reduced serum levels of TGF-β1 and PDGF[1]
- In a rat model of airway sodium transport dysfunction, intratracheal nebulization of Camostat Mesilate (FOY305) (0.1% formulation, 0.5 mL/rat, once daily for 7 days) reduced ENaC-mediated sodium absorption in the airway. It increased airway surface liquid volume by 35% and improved mucociliary clearance by 40%[3]

Channel-activating protease activity assay: Purified channel-activating protease was incubated with fluorogenic peptide substrate and different concentrations of Camostat Mesilate (FOY305) (1-100 μM) at 37°C for 1 hour. The fluorescence intensity of the cleaved substrate was measured using a fluorometer, and the protease inhibition rate was calculated[3]
- Viral protease activity assay: Recombinant SARS-CoV spike protein or Ebola virus glycoprotein was incubated with target protease, fluorogenic peptide substrate, and Camostat Mesilate (FOY305) (2-50 μM) at 37°C for 90 minutes. Fluorescence signals were recorded to evaluate the drug's inhibitory effect on protease-mediated peptide cleavage[4]

Pancreatic stellate cell assay: Rat PSCs were isolated and seeded in 96-well plates (1×10^3 cells/well) and 6-well plates. Camostat Mesilate (FOY305) (1-100 μM) was added, and cells were cultured for 72 hours (proliferation assay) or 7 days (activation assay). Cell viability was detected by MTT assay, and α-SMA/collagen expression was analyzed by Western blot and qPCR[1]
- Monocyte function assay: Human peripheral blood monocytes were isolated and seeded in transwell chambers or 24-well plates. Camostat Mesilate (FOY305) (5-50 μM) was added 1 hour before stimulation with pancreatic tissue extracts or LPS. Monocyte chemotaxis was quantified by counting migrated cells, and cytokine levels in the supernatant were measured by ELISA[1]
- ENaC function assay: Calu-3 cells were seeded on permeable filter supports to form confluent monolayers. Camostat Mesilate (FOY305) (10-100 μM) was added to the apical side, and ENaC activity was assessed by measuring amiloride-sensitive short-circuit current (Isc) using an Ussing chamber[3]
- Viral infection assay: Vero/Vero E6 cells were seeded in 24-well plates and infected with SARS-CoV, Ebola virus, or SARS-CoV-2 at a multiplicity of infection (MOI) of 0.1. Camostat Mesilate (FOY305) (5-50 μM) was added 1 hour post-infection, and cells were cultured for 48 hours. Viral load was quantified by qPCR or plaque assay[2][4]

Animal/Disease Models: 6-8 week old female balb/c (Bagg ALBino) mouse (lethal SARS-CoV infection model)[4]
Doses: 30 mg/kg
Route of Administration: Po; twice a day for 9 days
Experimental Results: Effective in protecting mice against death due to a lethal infection by SARS-CoV, with a survival rate of ∼60%.

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Pancreatic fibrosis rat model: Male Wistar rats (200-250 g) were intraperitoneal injected with DBTC to induce pancreatic fibrosis. One week after induction, rats were randomly divided into control and treatment groups. The treatment group received oral Camostat Mesilate (FOY305) (100 mg/kg) once daily for 4 weeks, while the control group received an equal volume of 0.5% carboxymethylcellulose sodium (CMC-Na). Rats were euthanized, and pancreatic tissues and serum samples were collected for histopathological and cytokine analysis[1]
- Airway sodium transport dysfunction rat model: Male Sprague-Dawley rats (220-250 g) were used. Camostat Mesilate (FOY305) was formulated as a 0.1% nebulization solution. Rats were subjected to intratracheal nebulization of 0.5 mL solution once daily for 7 days. Control rats received nebulized normal saline. After treatment, airway tissues were collected to measure ENaC activity and airway surface liquid volume[3]

In vitro toxicity: Carmustine mesylate (FOY305) showed low cytotoxicity to normal human pancreatic ductal cells and airway epithelial cells, with an IC50 value >200 μM[1][3]
- In vivo toxicity: In animal experiments, oral administration of 100 mg/kg or nebulized 0.1% formulation for 4-7 weeks did not cause significant weight loss, behavioral abnormalities, or changes in liver and kidney function indicators (ALT, AST, BUN, creatinine)[1][3]
- Clinically relevant side effects: This drug may cause mild gastrointestinal reactions (nausea, diarrhea) in clinical applications[1][2]

[1]. Gibo J, et al. Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity. Lab Invest. 2005;85(1):75‐89.
[2]. Uno Y. Camostat mesilate therapy for COVID-19 [published online ahead of print, 2020 Apr 29]. Intern Emerg Med. 2020;1‐2.
[3]. Coote K, et al. Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease. J Pharmacol Exp Ther. 2009;329(2):764‐774.
[4]. Zhou Y, Vedantham P, Lu K, et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res. 2015;116:76‐84.

Carmostat mesylate is a mesylate salt prepared from equimolar amounts of carmostat and mesylate. It is a serine protease inhibitor, approved for marketing in Japan in 1985 for the relief of acute symptoms associated with chronic pancreatitis. In 1994, it was approved for the treatment of postoperative reflux esophagitis. It possesses various activities including anticoronavirus, anti-inflammatory, antifibrinolytic, antihypertensive, antitumor, antiviral, and serine protease inhibition. It contains a carmostat (1+) ligand. Carmostat mesylate is the mesylate form of carmostat, a highly bioavailable synthetic serine protease inhibitor with anti-inflammatory, antifibrotic, and potential antiviral activities. Oral administration of carmostat and its metabolite 4-(4-guanidinobenzoyloxy)phenylacetic acid (FOY 251) inhibits the activity of various proteases, including trypsin, kallikrein, thrombin, and plasmin, as well as C1r and C1 esterases. Although the mechanism of action of carmustine has not been fully elucidated, it is known that activation of trypsinogen in the pancreas is a triggering response for pancreatitis. Carmustine can block the activation of trypsinogen into trypsin and the inflammatory cascade it triggers. Carmustine can also inhibit the expression of cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), as well as α-smooth muscle actin (α-SMA). This can alleviate pancreatic inflammation and fibrosis. In addition, carmustine may inhibit the activity of transmembrane serine protease 2 (TMPRSS2), a host cell serine protease that mediates viral invasion of influenza virus and coronavirus, thereby inhibiting viral infection and replication.

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Carmustine mesylate (FOY305) is a synthetic serine protease inhibitor that is used clinically to treat acute pancreatitis and chronic pancreatitis[1].
- Its core mechanism of action involves the inhibition of multiple proteases, thereby regulating cell activation, cytokine release, viral invasion, and ion channel function [1][3][4].
- This drug alleviates pancreatic fibrosis by inhibiting pancreatic stellate cell (PSC) activation and monocyte-mediated profibrotic responses, providing a treatment option for pancreatic fibrosis [1].
- It inhibits viral invasion by blocking protease-mediated cleavage of viral spike/glycoproteins, showing potential efficacy against coronaviruses (including COVID-19) and filamentous viruses [2][4].
- By targeting proteases that activate channels, camostat mesylate (FOY305) modulates ENaC function in the airways, which may be beneficial for diseases associated with impaired mucociliary clearance [3].

C20H22N4O5.CH4O3S

494.52

494.147

59721-29-8

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

5284360

White to off-white solid powder

634.6ºC at 760 mmHg

150-1550C

2.842

3

9

9

34

695

0

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

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)

4-(2-(2-(dimethylamino)-2-oxoethoxy)-2-oxoethyl)phenyl 4-guanidinobenzoate methanesulfonate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 12.5 mg/mL (25.28 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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