Camostat
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Camostat
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CAS No:
59721-28-7
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Formula:
C20H22N4O5
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Chemical Name:
Camostat
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Synonyms:
Benzeneacetic acid,4-[[4-[(aminoiminomethyl)amino]benzoyl]oxy]-,2-(dimethylamino)-2-oxoethyl ester;Camostat
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CAS No:
Description
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 derives from 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.
Camostat Basic Attributes
398.4
398.15901982
0FD207WKDU
DTXSID6044010
C73213
B - Blood and blood forming organs
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.
Camostat mesylate is 25.8-28.2% protein bound to human serum proteins _in vitro_.
Drug Information
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.
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.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). (See all compounds classified as Protease Inhibitors.)|Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds. (See all compounds classified as Trypsin Inhibitors.)
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.
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.
The half life of camostat mesylate is 3.8-4.7h.
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.
camostat
Computed Properties
Molecular Weight:398.4
XLogP3:1.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:9
Exact Mass:398.15901982
Monoisotopic Mass:398.15901982
Topological Polar Surface Area:137
Heavy Atom Count:29
Complexity:602
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes