Camostat

Last updated
Camostat
Camostat.svg
Clinical data
Trade names Foipan
Other namesFOY-305
AHFS/Drugs.com International Drug Names
Routes of
administration 		Oral
ATC code
Legal status
Legal status
  • US:Not FDA approved
  • In general: ℞ (Prescription only)
Identifiers
  • N,N-Dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)phenylacetate
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C20H22N4O5
Molar mass 398.419 g·mol−1
3D model (JSmol)
  • CN(C)C(=O)COC(=O)CC1=CC=C(C=C1)OC(=O)C2=CC=C(C=C2)N=C(N)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) Yes check.svgY
  • Key:XASIMHXSUQUHLV-UHFFFAOYSA-N Yes check.svgY
   (verify)

Camostat is a serine protease inhibitor. Serine protease enzymes have a variety of functions in the body, and so camostat has a diverse range of uses. Camostat is approved in Japan for the treatment of chronic pancreatitis and postoperative reflux esophagitis. [1] [2] The oral proteolytic enzyme inhibitor has been on the market since 1985 under the trade name Foipan Tablets. The manufacturer is Ono Pharmaceutical. The drug is used in the treatment of some forms of cancer and is also effective against some viral infections, as well as inhibiting fibrosis in liver or kidney disease or pancreatitis. [3] [4] [5] [6] [7]

Contents

Pharmacology

It is an inhibitor of the enzyme transmembrane protease, serine 2 (TMPRSS2). For chronic pancreatitis camostat's typical dose is 600 mg daily, for postoperative reflux esophagitis 300 mg are taken. The daily dose is split in 3 doses and taken after each meal. [1] [8]

Side effects

As side effects allergic reactions including anaphylaxis, hypersensitivity, hyperkalemia, platelet and leukocyte depletion, liver dysfunction, jaundice have been reported. [9]

COVID-19

Camostat 100mg tablets (Japanese Blister) Camostat,INN; Kai Fa kodo FOY-305 kamosutatsuto 3441.jpg
Camostat 100mg tablets (Japanese Blister)

Inhibition of TMPRSS2 partially blocked infection by SARS-CoV and Human coronavirus NL63 in HeLa cell cultures. [10] Another in vitro study showed that camostat significantly reduces the infection of Calu-3 lung cells by SARS-CoV-2, the virus responsible for COVID-19. [11] [12] It is currently in many Phase 1 and Phase 2 clinical trials. [13] [14]

Camostat decreased CRP levels better compared to Lopinavir/Ritonavir in a small study of mild COVID-19 patients. [15] Camostat decreased COVID-19 severity, improved inflammatory markers and oxygenation compared to hydroxychloroquine treated patients. [16] [12]

A study of 205 COVID-19 patients treated with Camostat, carried out at Aarhus University Hospital in Denmark and concluding in April 2021, showed no noticeable effects of Camostat on duration of hospitalisation or severity of the cases, but noted that higher doses (the study used 600 mg Camostat daily dosage) might still have a possible effect. [17]

On July 1, 2021, the AIDS Clinical Trials Group announced that the Camostat group on the "ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial" would not be moving forward to Phase 3. The trial demonstrated no safety concerns but also no changes in viral shedding or symptom improvement. [18]

Related Research Articles

Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS, hepatitis C and COVID-19. These protease inhibitors prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.

<span class="mw-page-title-main">Ritonavir</span> Antiretroviral medication

Ritonavir, sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor, though it now mainly serves to boost the potency of other protease inhibitors. It may also be used in combination with other medications to treat hepatitis C and COVID-19. It is taken by mouth. Tablets of ritonavir are not bioequivalent to capsules, as the tablets may result in higher peak plasma concentrations.

<span class="mw-page-title-main">Nelfinavir</span> Antiretroviral drug

Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is almost always used in combination with other antiretroviral drugs.

<span class="mw-page-title-main">Fosamprenavir</span> Chemical compound

Fosamprenavir (FPV), sold under the brand names Lexiva and Telzir, is a medication used to treat HIV/AIDS. It is a prodrug of the protease inhibitor and antiretroviral drug amprenavir. It is marketed by ViiV Healthcare as the calcium salt.

<span class="mw-page-title-main">Lopinavir</span> Chemical compound

Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir (lopinavir/ritonavir).

<span class="mw-page-title-main">Umifenovir</span> Chemical compound

Umifenovir, sold under the brand name Arbidol, is an antiviral medication for the treatment of influenza and COVID infections used in Russia and China. The drug is manufactured by Pharmstandard. It is not approved by the U.S. Food and Drug Administration (FDA) for the treatment or prevention of influenza.

<span class="mw-page-title-main">TMPRSS2</span> Protein-coding gene in the species Homo sapiens

Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene. It belongs to the TMPRSS family of proteins, whose members are transmembrane proteins which have a serine protease activity. The TMPRSS2 protein is found in high concentration in the cell membranes of epithelial cells of the lung and of the prostate, but also in the heart, liver and gastrointestinal tract.

<span class="mw-page-title-main">Nafamostat</span> Chemical compound

Nafamostatmesylate (INN), a synthetic serine protease inhibitor, it is a short-acting anticoagulant, and is also used for the treatment of pancreatitis. It also has some potential antiviral and anti-cancer properties. Nafamostat is a fast-acting proteolytic inhibitor and used during hemodialysis to prevent the proteolysis of fibrinogen into fibrin. The mechanism of action of Nafamostat is as a slow tight-binding substrate, trapping the target protein in the acyl-enzyme intermediate form, resulting in apparent observed inhibition.

<span class="mw-page-title-main">Lopinavir/ritonavir</span> Combination medication for HIV/AIDS

Lopinavir/ritonavir (LPV/r), sold under the brand name Kaletra among others, is a fixed-dose combination antiretroviral medication for the treatment and prevention of HIV/AIDS. It combines lopinavir with a low dose of ritonavir. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth as a tablet, capsule, or solution.

<span class="mw-page-title-main">Simeprevir</span> Chemical compound

Simeprevir, sold under the brand name Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with include sofosbuvir or ribavirin and peginterferon-alfa. Cure rates are in 80s to 90s percent. It may be used in those who also have HIV/AIDS. It is taken by mouth once daily for typically 12 weeks.

<span class="mw-page-title-main">3C-like protease</span> Class of enzymes

The 3C-like protease (3CLpro) or main protease (Mpro), formally known as C30 endopeptidase or 3-chymotrypsin-like protease, is the main protease found in coronaviruses. It cleaves the coronavirus polyprotein at eleven conserved sites. It is a cysteine protease and a member of the PA clan of proteases. It has a cysteine-histidine catalytic dyad at its active site and cleaves a Gln–(Ser/Ala/Gly) peptide bond.

<span class="mw-page-title-main">Narlaprevir</span> Chemical compound

Narlaprevir, is an inhibitor of NS3/4A serine protease, intended for the treatment of chronic hepatitis C caused by genotype 1 virus in combination with other antiviral drugs.

<span class="mw-page-title-main">COVID-19 drug repurposing research</span> Drug repurposing research related to COVID-19

Drug repositioning is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine and convalescent plasma transfusion.

<span class="mw-page-title-main">COVID-19 drug development</span> Preventative and therapeutic medications for COVID-19 infection

COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.

<span class="mw-page-title-main">Chloroquine and hydroxychloroquine during the COVID-19 pandemic</span> Early experimental treatment efforts during the start of COVID-19 pandemic

Chloroquine and hydroxychloroquine are anti-malarial medications also used against some auto-immune diseases. Chloroquine, along with hydroxychloroquine, was an early experimental treatment for COVID-19. Neither drug prevents SARS-CoV-2 infection.

<span class="mw-page-title-main">Nirmatrelvir</span> COVID-19 antiviral medication

Nirmatrelvir is an antiviral medication developed by Pfizer which acts as an orally active 3C-like protease inhibitor. It is part of a nirmatrelvir/ritonavir combination used to treat COVID-19 and sold under the brand name Paxlovid.

<span class="mw-page-title-main">Lufotrelvir</span> Chemical compound

Lufotrelvir (PF-07304814) is an antiviral drug developed by Pfizer which acts as a 3CL protease inhibitor. It is a prodrug with the phosphate group being cleaved in vivo to yield the active agent PF-00835231. Lufotrelvir is in human clinical trials for the treatment of COVID-19, and shows good activity against COVID-19 including several variant strains, but unlike the related drug nirmatrelvir it is not orally active and must be administered by intravenous infusion, and so has been the less favoured candidate for clinical development overall.

<span class="mw-page-title-main">Nirmatrelvir/ritonavir</span> Antiviral combination medication

Nirmatrelvir/ritonavir, sold under the brand name Paxlovid, is a co-packaged medication used as a treatment for COVID‑19. It contains the antiviral medications nirmatrelvir and ritonavir and was developed by Pfizer. Both components are protease inhibitors: nirmatrelvir inhibits SARS-CoV-2 main protease, while ritonavir inhibits HIV-1 protease, and is additionally a strong CYP3A inhibitor. It is taken by mouth.

<span class="mw-page-title-main">Ensitrelvir</span> COVID-19 SARS-CoV-2 3CL-protease-inhibitor antiviral drug

Ensitrelvir, sold under the brand name Xocova is an antiviral medication used as a treatment for COVID-19. It was developed by Shionogi in partnership with Hokkaido University and acts as an orally active 3C-like protease inhibitor. It is taken by mouth.

<span class="mw-page-title-main">Olgotrelvir</span> COVID-19 SARS-CoV-2 3CL-protease-inhibitor antiviral drug

Olgotrelvir (STI-1558) is an experimental antiviral medication being studied to evaluate its potential as a treatment for COVID-19. It is believed to work by inhibiting the SARS-CoV-2 main protease (Mpro), a key enzyme that SARS-CoV-2 needs to replicate, and by blocking viral entry.

References

  1. 1 2 "FOIPAN® Tablets 100mg" (PDF). Ono Pharmaceutical Co., Ltd.
  2. ↑ "Camostat". drugs.com.
  3. ↑ Okuno M, Kojima S, Akita K, Matsushima-Nishiwaki R, Adachi S, Sano T, et al. (January 2002). "Retinoids in liver fibrosis and cancer". Frontiers in Bioscience. 7 (4): d204–d218. doi:10.2741/A775. PMID   11779708.
  4. ↑ Hsieh HP, Hsu JT (2007). "Strategies of development of antiviral agents directed against influenza virus replication" (PDF). Current Pharmaceutical Design. 13 (34): 3531–3542. doi:10.2174/138161207782794248. PMID   18220789.
  5. ↑ Kitamura K, Tomita K (February 2012). "Proteolytic activation of the epithelial sodium channel and therapeutic application of a serine protease inhibitor for the treatment of salt-sensitive hypertension". Clinical and Experimental Nephrology. 16 (1): 44–48. doi:10.1007/s10157-011-0506-1. PMID   22038264. S2CID   6522071.
  6. ↑ Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R, Nunneley JW, et al. (April 2015). "Protease inhibitors targeting coronavirus and filovirus entry". Antiviral Research. 116: 76–84. doi:10.1016/j.antiviral.2015.01.011. PMC   4774534 . PMID   25666761.
  7. ↑ Ueda M, Uchimura K, Narita Y, Miyasato Y, Mizumoto T, Morinaga J, et al. (2015). "The serine protease inhibitor camostat mesilate attenuates the progression of chronic kidney disease through its antioxidant effects". Nephron. 129 (3): 223–232. doi:10.1159/000375308. PMID   25766432. S2CID   207652863.
  8. ↑ Breining P, Frølund AL, Højen JF, Gunst JD, Staerke NB, Saedder E, Cases-Thomas M, Little P, Nielsen LP, Søgaard OS, Kjolby M (February 2021). "Camostat mesylate against SARS-CoV-2 and COVID-19-Rationale, dosing and safety". Basic & Clinical Pharmacology & Toxicology. 128 (2): 204–212. doi: 10.1111/bcpt.13533 . PMID   33176395.
  9. ↑ "医療用医薬品 : カモスタットメシル酸塩 (カモスタットメシル酸塩錠100mg「日医工」)". KEGG (in Japanese). Retrieved 2021-02-05.
  10. ↑ Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S (June 2012). "Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry". Journal of Virology. 86 (12): 6537–6545. doi:10.1128/JVI.00094-12. PMC   3393535 . PMID   22496216.
  11. ↑ Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. (April 2020). "SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor". Cell. 181 (2): 271–280.e8. doi:10.1016/j.cell.2020.02.052. PMC   7102627 . PMID   32142651.
  12. 1 2 Jackson CB, Farzan M, Chen B, Choe H (January 2022). "Mechanisms of SARS-CoV-2 entry into cells". Nature Reviews. Molecular Cell Biology. 23 (1): 3–20. doi:10.1038/s41580-021-00418-x. PMC   8491763 . PMID   34611326.
  13. ↑ Clinical trial number NCT04374019 for "Novel Agents for Treatment of High-risk COVID-19 Positive Patients" at ClinicalTrials.gov
  14. ↑ "Search of: camostat - covid - List Results". ClinicalTrials.gov. Retrieved 2021-02-04.
  15. ↑ Choi JP, Kim HJ, Han J, Park S, Han J (2020-12-15). Foistar(Camostat mesylate) associated with the significant decrease in CRP levels compared to Kaletra(Lopinavir/Ritonavir) treatment in Korean mild COVID-19 pneumonic patients (Report). Infectious Diseases (except HIV/AIDS). doi:10.1101/2020.12.10.20240689.
  16. ↑ Hofmann-Winkler H, Moerer O, Alt-Epping S, Bräuer A, Büttner B, Müller M, et al. (November 2020). "Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation". Critical Care Explorations. 2 (11): e0284. doi:10.1097/CCE.0000000000000284. hdl:20.500.11850/460814. PMC   7671878 . PMID   33225308.
  17. ↑ "Middel mod halsbrand bremsede ikke Covid-19". newsroom.au.dk (in Danish). Retrieved 2021-04-28.
  18. ↑ "ACTG announces Camostat will not advance to phase 3 in outpatient treatment study for COVID-19". EurekAlert!. Retrieved 2021-07-01.
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