Identification
- Generic Name
- Nafamostat
- DrugBank Accession Number
- DB12598
- Background
Nafamostat is a synthetic serine protease inhibitor that is commonly formulated with hydrochloric acid due to its basic properties. It has been used in trials studying the prevention of Liver Transplantation and Postreperfusion Syndrome. The use of nafamostat in Asian countries is approved as an anticoagulant therapy for patients undergoing continuous renal replacement therapy due to acute kidney injury.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Nafamostat (DB12598)
- Weight
- Average: 347.378
Monoisotopic: 347.138224807 - Chemical Formula
- C19H17N5O2
- Synonyms
- Nafamostat
- Nafamostatum
- p-Guanidinobenzoic acid ester with 6-hydroxy-2-naphthamidine
Pharmacology
- Indication
Used as an anticoagulant in patients with disseminative blood vessel coagulation, hemorrhagic lesions, and hemorrhagic tendencies. It prevents blood clot formation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Nafamostat is a fast-acting proteolytic inhibitor used during hemodialysis to prevent the proteolysis of fibrinogen into fibrin by competitively inhibiting several serine proteases including thrombin. It improves acute pancreatitis and prevents blood clot formation during extracorporeal circulation and has an anti-inflammatory effect in vitro. A study suggets that nafamostat has a neuroprotective role during ischemia-induced brain injury from antithrombin activity 5.
- Mechanism of action
Nafamostat mesilate inhibits various enzyme systems, such as coagulation and fibrinolytic systems (thrombin, Xa, and XIIa), the kallikrein–kinin system, the complement system, pancreatic proteases and activation of protease-activated receptors (PARs) 6. Nafamostat inhibits lipopolysaccharide-induced nitric oxide production, apoptosis, and interleukin (IL)-6 and IL-8 levels in cultured human trophoblasts. It is shown to act as an antioxidant in TNF-α-induced ROS production 2.
Target Actions Organism AProthrombin inhibitorHumans ACoagulation factor X inhibitorHumans ACoagulation factor XII inhibitorHumans ATrypsin-1 inhibitorHumans AKallikrein-1 inhibitorHumans UIntercellular adhesion molecule 1 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Nafamostat is mainly hydrolyzed by hepatic carboxyesterase and long-chain acyl-CoA hydrolase in human liver cytosol. Main metabolites are p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol (AN) as inactive protease inhibitors.
- Route of elimination
Two metabolites of NM, p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol (AN), are renally excreted. Nafamostat accumulates in the kidneys.
- Half-life
Approximately 8 minutes 4
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Reported incidences of agranulocytosis, hyperkalemia, and anaphylaxis. The use of nafamostat has been reported to cause cardiac arrest in patients receiving dialysis due to a sudden change in the patient's condition such as dyspnea. A study suggests that the drug and its metabolites may inhibit the amiloride-sensitive sodium (Na) conductance at the collecting ducts, resulting in an inhibition of K secretion and hyperkalemia 7. Reported LD50 value from intravenous administration in rats is 16.4mg/kg.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of bleeding can be increased when Abciximab is combined with Nafamostat. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Nafamostat. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when Nafamostat is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Nafamostat. Acetylsalicylic acid Acetylsalicylic acid may increase the anticoagulant activities of Nafamostat. - Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Nafamostat mesylate 1D2T74921W 82956-11-4 SRXKIZXIRHMPFW-UHFFFAOYSA-N - International/Other Brands
- Berabu (Tobishi Pharmaceutical, Japan) / Buipel (Teva Seiyaku, Japan) / Buseron (Sawai Seiyaku, Japan) / Coahibitor (AY Pharma, Japan) / Famoset (Towa Yakuhin, Japan) / Futhan (Torii Yakuhin, Japan) / Nafaston (Fuji Seiyaku, Japan) / Nafatat (Nichi-Iko Pharmaceutical, Japan) / Namostatt (Pola Pharma, Japan) / Naotamin (Asahi Kasei Pharma, Japan) / Opsun (Sanwa Kagaku, Japan) / Pathron (Nipro, Japan) / Ronastat (Koa Isei, Japan)
Categories
- Drug Categories
- Amidines
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anticoagulants
- Antirheumatic Agents
- Complement Inactivating Agents
- Enzyme Inhibitors
- Fibrinolysin, antagonists & inhibitors
- Hematologic Agents
- Immunologic Factors
- Kallikreins, antagonists & inhibitors
- OCT1 substrates
- OCT2 Substrates
- Peripheral Nervous System Agents
- Protease Inhibitors
- Sensory System Agents
- Serine Protease Inhibitors
- Trypsin Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as guanidinobenzoic acids and derivatives. These are aromatic compounds containing a guanidine group linked to the benzene ring of a benzoic acid (or a derivative thereof).
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzoic acids and derivatives
- Direct Parent
- Guanidinobenzoic acids and derivatives
- Alternative Parents
- Naphthalenes / Benzoic acid esters / Benzoyl derivatives / Guanidines / Carboxylic acid esters / Propargyl-type 1,3-dipolar organic compounds / Monocarboxylic acids and derivatives / Carboximidamides / Carboxamidines / Organopnictogen compounds show 3 more
- Substituents
- Amidine / Aromatic homopolycyclic compound / Benzoate ester / Benzoyl / Carboximidamide / Carboxylic acid amidine / Carboxylic acid derivative / Carboxylic acid ester / Guanidine / Guanidinobenzoic acid or derivatives show 11 more
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Y25LQ0H97D
- CAS number
- 81525-10-2
- InChI Key
- MQQNFDZXWVTQEH-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H17N5O2/c20-17(21)14-2-1-13-10-16(8-5-12(13)9-14)26-18(25)11-3-6-15(7-4-11)24-19(22)23/h1-10H,(H3,20,21)(H4,22,23,24)
- IUPAC Name
- 6-carbamimidoylnaphthalen-2-yl 4-carbamimidamidobenzoate
- SMILES
- NC(=N)NC1=CC=C(C=C1)C(=O)OC1=CC2=C(C=C1)C=C(C=C2)C(N)=N
References
- General References
- Maruyama Y, Yoshida H, Uchino S, Yokoyama K, Yamamoto H, Takinami M, Hosoya T: Nafamostat mesilate as an anticoagulant during continuous veno-venous hemodialysis: a three-year retrospective cohort study. Int J Artif Organs. 2011 Jul;34(7):571-6. doi: 10.5301/IJAO.2011.8535. [Article]
- Kang MW, Song HJ, Kang SK, Kim Y, Jung SB, Jee S, Moon JY, Suh KS, Lee SD, Jeon BH, Kim CS: Nafamostat Mesilate Inhibits TNF-alpha-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production. Korean J Physiol Pharmacol. 2015 May;19(3):229-34. doi: 10.4196/kjpp.2015.19.3.229. Epub 2015 Apr 30. [Article]
- Choi S, Kwon HJ, Song HJ, Choi SW, Nagar H, Piao S, Jung SB, Jeon BH, Kim DW, Kim CS: Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway. Korean J Physiol Pharmacol. 2016 Sep;20(5):539-45. doi: 10.4196/kjpp.2016.20.5.539. Epub 2016 Aug 26. [Article]
- Choi JY, Kang YJ, Jang HM, Jung HY, Cho JH, Park SH, Kim YL, Kim CD: Nafamostat Mesilate as an Anticoagulant During Continuous Renal Replacement Therapy in Patients With High Bleeding Risk: A Randomized Clinical Trial. Medicine (Baltimore). 2015 Dec;94(52):e2392. doi: 10.1097/MD.0000000000002392. [Article]
- Chen T, Wang J, Li C, Zhang W, Zhang L, An L, Pang T, Shi X, Liao H: Nafamostat mesilate attenuates neuronal damage in a rat model of transient focal cerebral ischemia through thrombin inhibition. Sci Rep. 2014 Jul 2;4:5531. doi: 10.1038/srep05531. [Article]
- Kim HS, Lee KE, Oh JH, Jung CS, Choi D, Kim Y, Jeon JS, Han DC, Noh H: Cardiac arrest caused by nafamostat mesilate. Kidney Res Clin Pract. 2016 Sep;35(3):187-9. doi: 10.1016/j.krcp.2015.10.003. Epub 2015 Nov 12. [Article]
- Muto S, Imai M, Asano Y: Mechanisms of the hyperkalaemia caused by nafamostat mesilate: effects of its two metabolites on Na+ and K+ transport properties in the rabbit cortical collecting duct. Br J Pharmacol. 1994 Jan;111(1):173-8. [Article]
- FDA Executive Summary [Link]
- External Links
- PubChem Compound
- 4413
- PubChem Substance
- 347828816
- ChemSpider
- 4260
- BindingDB
- 50063698
- ChEBI
- 135466
- ChEMBL
- CHEMBL273264
- ZINC
- ZINC000003874467
- PDBe Ligand
- 7RF
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Nafamostat
- PDB Entries
- 7vm7
- MSDS
- Download (29.4 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Prevention Liver Transplantation / Postreperfusion Syndrome 1 4 Completed Treatment Acute Kidney Injury (AKI) 2 4 Not Yet Recruiting Treatment Nafamostat Mesilate / Sepsis / Sepsis-induced Coagulopathy 1 3 Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) 1 3 Unknown Status Not Available Acute Kidney Injury (AKI) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0341 mg/mL ALOGPS logP 1.91 ALOGPS logP 2.52 Chemaxon logS -4 ALOGPS pKa (Strongest Basic) 11.32 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 138.07 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 122.12 m3·mol-1 Chemaxon Polarizability 36.48 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-03di-0900000000-ca2f2f9e08a54703578e Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000t-0009000000-6eb33cc8cd7cb4de16bc Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0udj-0029000000-0a623f58ae16e62cdaa0 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-2009000000-1a18391888c237755247 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001r-0389000000-d63054a46b1c892023dc Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9031000000-9193a082f90abfc29b48 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-1900000000-f2cfae87f4a152e0e2ca Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 203.8852765 predictedDarkChem Lite v0.1.0 [M-H]- 177.02306 predictedDeepCCS 1.0 (2019) [M+H]+ 203.8004765 predictedDarkChem Lite v0.1.0 [M+H]+ 179.38106 predictedDeepCCS 1.0 (2019) [M+Na]+ 203.0080765 predictedDarkChem Lite v0.1.0 [M+Na]+ 186.38634 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Thrombospondin receptor activity
- Specific Function
- Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
- Gene Name
- F2
- Uniprot ID
- P00734
- Uniprot Name
- Prothrombin
- Molecular Weight
- 70036.295 Da
References
- Iwaki M, Ino Y, Motoyoshi A, Ozeki M, Sato T, Kurumi M, Aoyama T: Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats. Jpn J Pharmacol. 1986 Jun;41(2):155-62. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
- Gene Name
- F10
- Uniprot ID
- P00742
- Uniprot Name
- Coagulation factor X
- Molecular Weight
- 54731.255 Da
References
- Baek NN, Jang HR, Huh W, Kim YG, Kim DJ, Oh HY, Lee JE: The role of nafamostat mesylate in continuous renal replacement therapy among patients at high risk of bleeding. Ren Fail. 2012;34(3):279-85. doi: 10.3109/0886022X.2011.647293. Epub 2012 Jan 17. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII t...
- Gene Name
- F12
- Uniprot ID
- P00748
- Uniprot Name
- Coagulation factor XII
- Molecular Weight
- 67791.53 Da
References
- Baek NN, Jang HR, Huh W, Kim YG, Kim DJ, Oh HY, Lee JE: The role of nafamostat mesylate in continuous renal replacement therapy among patients at high risk of bleeding. Ren Fail. 2012;34(3):279-85. doi: 10.3109/0886022X.2011.647293. Epub 2012 Jan 17. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form aga...
- Gene Name
- PRSS1
- Uniprot ID
- P07477
- Uniprot Name
- Trypsin-1
- Molecular Weight
- 26557.88 Da
References
- Ramjee MK, Henderson IM, McLoughlin SB, Padova A: The kinetic and structural characterization of the reaction of nafamostat with bovine pancreatic trypsin. Thromb Res. 2000 Jun 15;98(6):559-69. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.
- Gene Name
- KLK1
- Uniprot ID
- P06870
- Uniprot Name
- Kallikrein-1
- Molecular Weight
- 28889.425 Da
References
- Iwaki M, Ino Y, Motoyoshi A, Ozeki M, Sato T, Kurumi M, Aoyama T: Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats. Jpn J Pharmacol. 1986 Jun;41(2):155-62. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Virus receptor activity
- Specific Function
- ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial api...
- Gene Name
- ICAM1
- Uniprot ID
- P05362
- Uniprot Name
- Intercellular adhesion molecule 1
- Molecular Weight
- 57824.785 Da
References
- Kang MW, Song HJ, Kang SK, Kim Y, Jung SB, Jee S, Moon JY, Suh KS, Lee SD, Jeon BH, Kim CS: Nafamostat Mesilate Inhibits TNF-alpha-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production. Korean J Physiol Pharmacol. 2015 May;19(3):229-34. doi: 10.4196/kjpp.2015.19.3.229. Epub 2015 Apr 30. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Secondary active organic cation transmembrane transporter activity
- Specific Function
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Li Q, Sai Y, Kato Y, Muraoka H, Tamai I, Tsuji A: Transporter-mediated renal handling of nafamostat mesilate. J Pharm Sci. 2004 Feb;93(2):262-72. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Li Q, Sai Y, Kato Y, Muraoka H, Tamai I, Tsuji A: Transporter-mediated renal handling of nafamostat mesilate. J Pharm Sci. 2004 Feb;93(2):262-72. [Article]
Drug created at October 20, 2016 23:07 / Updated at February 21, 2021 18:53