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Chemical Structure| 59721-29-8 Chemical Structure| 59721-29-8

Structure of Camostat Mesylate
CAS No.: 59721-29-8

Chemical Structure| 59721-29-8

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Camostat mesylate is a trypsin-like protease inhibitor, inhibits airway epithelial sodium channel (ENaC) function with IC50 of 50 nM, less potent to trypsin, prostasin and matriptase.

Synonyms: Camostat mesilate; FOY305; Foipan

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Product Citations

Product Citations

Frauke Assmus ; Jean-Sélim Driouich ; Rana Abdelnabi ; Laura Vangeel ; Franck Touret ; Ayorinde Adehin , et al.

Abstract: In the absence of drugs to treat or prevent COVID-19, drug repurposing can be a valuable strategy. Despite a substantial number of clinical trials, drug repurposing did not deliver on its promise. While success was observed with some repurposed drugs (e.g., remdesivir, dexamethasone, tocilizumab, baricitinib), others failed to show clinical efficacy. One reason is the lack of clear translational processes based on adequate preclinical profiling before clinical evaluation. Combined with limitations of existing in vitro and in vivo models, there is a need for a systematic approach to urgent antiviral drug development in the context of a global pandemic. We implemented a methodology to test repurposed and experimental drugs to generate robust preclinical evidence for further clinical development. This translational drug development platform comprises in vitro, ex vivo, and in vivo models of SARS-CoV-2, along with pharmacokinetic modeling and simulation approaches to evaluate exposure levels in plasma and target organs. Here, we provide examples of identified repurposed antiviral drugs tested within our multidisciplinary collaboration to highlight lessons learned in urgent antiviral drug development during the COVID-19 pandemic. Our data confirm the importance of assessing in vitro and in vivo potency in multiple assays to boost the translatability of pre-clinical data. The value of pharmacokinetic modeling and simulations for compound prioritization is also discussed. We advocate the need for a standardized translational drug development platform for mild-to-moderate COVID-19 to generate preclinical evidence in support of clinical trials. We propose clear prerequisites for progression of drug candidates for repurposing into clinical trials. Further research is needed to gain a deeper understanding of the scope and limitations of the presented translational drug development platform.

Keywords: COVID-19 ; drug repurposing ; translational medicine ; pandemics ; clinical trials

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Alternative Products

Product Details of Camostat Mesylate

CAS No. :59721-29-8
Formula : C21H26N4O8S
M.W : 494.52
SMILES Code : 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
Synonyms :
Camostat mesilate; FOY305; Foipan
MDL No. :MFCD00941410
InChI Key :FSEKIHNIDBATFG-UHFFFAOYSA-N
Pubchem ID :5284360

Safety of Camostat Mesylate

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H319-H372-H410
Precautionary Statements:P501-P273-P260-P270-P264-P280-P391-P314-P337+P313-P305+P351+P338-P301+P312+P330
Class:9
UN#:3077
Packing Group:

Isoform Comparison

Biological Activity

Target
  • Sodium Channel

    epithelial sodium channel (ENaC), IC50:50 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
PK 10.4 nM (IC50) Determination of Camostat's inhibitory effect on PK, IC50 of 10.4 nM J Virol. 2021 Sep 9;95(19):e0086121.
HEK-293T 142 nM (IC50) Confirm Camostat inhibits TMPRSS2 activity Chem Sci. 2020 Nov 13;12(3):983-992.
Cathepsin G (CatG) 80 µg/mL 1 hour Analyze the inhibitory capacity of camostat towards CatG proteolytic activity Pharmaceuticals (Basel). 2022 Apr 20;15(5):500.
Proteinase 3 (PR3) 0 to 1000 µM 15 minutes Analyze the inhibitory capacity of camostat towards PR3 proteolytic activity Pharmaceuticals (Basel). 2022 Apr 20;15(5):500.
Proteinase 3 (PR3) 40 µg/mL 15 minutes Analyze the inhibitory capacity of camostat towards PR3 proteolytic activity Pharmaceuticals (Basel). 2022 Apr 20;15(5):500.
Neutrophil Elastase (NE) 40 µg/mL 15 minutes Analyze the inhibitory capacity of camostat towards NE proteolytic activity Pharmaceuticals (Basel). 2022 Apr 20;15(5):500.
Calu-3 cells 0.01, 0.1, 1, 10, 100 µM 2 hours Evaluate the inhibitory effect of Camostat mesylate on SARS-2-S-driven cell entry EBioMedicine. 2021 Mar;65:103255.
BHK-21 cells 100 µM 2 hours Evaluate the inhibitory effect of Camostat mesylate on SARS-2-S-driven cell entry EBioMedicine. 2021 Mar;65:103255.
Primary human lung cells 1-500 µM 2 hours pretreatment To evaluate the importance of TMPRSS2 for SARS-2-S-driven cell entry, camostat mesylate significantly reduced SARS-2-S-driven entry Cell. 2020 Apr 16;181(2):271-280.e8.
Calu-3 cells 1-500 µM 2 hours pretreatment To evaluate the importance of TMPRSS2 for SARS-2-S-driven cell entry, camostat mesylate significantly reduced SARS-2-S-driven entry Cell. 2020 Apr 16;181(2):271-280.e8.
Vero-TMPRSS2 cells 1-500 µM 2 hours pretreatment To evaluate the importance of TMPRSS2 for SARS-2-S-driven cell entry, camostat mesylate partially blocked SARS-2-S-driven entry Cell. 2020 Apr 16;181(2):271-280.e8.
Caco-2 cells 1-500 µM 2 hours pretreatment To evaluate the importance of TMPRSS2 for SARS-2-S-driven cell entry, camostat mesylate partially blocked SARS-2-S-driven entry Cell. 2020 Apr 16;181(2):271-280.e8.
Trypsin 9.3 nM (IC50) Determination of Camostat's inhibitory effect on trypsin, IC50 of 9.3 nM J Virol. 2021 Sep 9;95(19):e0086121.
Matriptase 21.1 nM (IC50) Determination of Camostat's inhibitory effect on matriptase, IC50 of 21.1 nM J Virol. 2021 Sep 9;95(19):e0086121.
FXIa 44.1 nM (IC50) Determination of Camostat's inhibitory effect on FXIa, IC50 of 44.1 nM J Virol. 2021 Sep 9;95(19):e0086121.
MuPA 100.4 nM (IC50) Determination of Camostat's inhibitory effect on muPA, IC50 of 100.4 nM J Virol. 2021 Sep 9;95(19):e0086121.
UPA 86.4 nM (IC50) Determination of Camostat's inhibitory effect on uPA, IC50 of 86.4 nM J Virol. 2021 Sep 9;95(19):e0086121.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Pancreatic growth model Oral 400 mg/kg/day Once daily for 10 days To assess the effects of camostate on pancreatic growth and plasma CCK concentration in mice. The results showed that chronic camostate feeding significantly increased pancreatic weight, protein and DNA content, and markedly elevated plasma CCK concentration. Gut. 1987;28 Suppl(Suppl):63-9

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT06794593 Chronic Kidney Disease(CKD) PHASE2 RECRUITING 2027-02-28 Department of Nephrology, Oden... More >>se University Hospital, Odense, 5000, Denmark Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.02mL

0.40mL

0.20mL

10.11mL

2.02mL

1.01mL

20.22mL

4.04mL

2.02mL

References

[1]Coote K, Atherton-Watson HC, et al. Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease. J Pharmacol Exp Ther. 2009 May;329(2):764-74.

[2]Okuno M, Akita K, et al. Prevention of rat hepatic fibrosis by the protease inhibitor, camostat mesilate, via reduced generation of active TGF-beta. Gastroenterology. 2001 Jun;120(7):1784-800.

[3]Coote K, Atherton-Watson HC, Sugar R, Young A, MacKenzie-Beevor A, Gosling M, Bhalay G, Bloomfield G, Dunstan A, Bridges RJ, Sabater JR, Abraham WM, Tully D, Pacoma R, Schumacher A, Harris J, Danahay H. Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease. J Pharmacol Exp Ther. 2009 May;329(2):764-74

[4]Gibo J, Ito T, Kawabe K, Hisano T, Inoue M, Fujimori N, Oono T, Arita Y, Nawata H. Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity. Lab Invest. 2005 Jan;85(1):75-89

[5]Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R Jr, Nunneley JW, Barnard D, Pöhlmann S, McKerrow JH, Renslo AR, Simmons G. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res. 2015 Apr;116:76-84

[6]Yuan L, Li M, Zhang Z, Li W, Jin W, Wang M. Camostat mesilate inhibits pro-inflammatory cytokine secretion and improves cell viability by regulating MFGE8 and HMGN1 in lipopolysaccharide-stimulated DF-1 chicken embryo fibroblasts. PeerJ. 2021 Aug 26;9:e12053

 

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