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Nafamostat

PubChem CID
4413
Structure
Nafamostat_small.png
Nafamostat_3D_Structure.png
Molecular Formula
Synonyms
  • Nafamostat
  • 81525-10-2
  • Nafamostat [INN]
  • Nafamstat
  • (6-carbamimidoylnaphthalen-2-yl) 4-(diaminomethylideneamino)benzoate
Molecular Weight
347.4 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-25
  • Modify:
    2025-02-01
Description
Nafamostat is a member of benzoic acids and a member of guanidines.
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.
Nafamostat is a broad-spectrum, synthetic serine protease inhibitor, with anticoagulant, anti-inflammatory, mucus clearing, and potential antiviral activities. Upon administration, nafamostat inhibits the activities of a variety of proteases, including thrombin, plasmin, kallikrein, trypsin, and Cl esterase in the complement system, and factors VIIa, Xa, and XIIa in the coagulation system. Although the mechanism of action of nafamostat is not fully understood, trypsinogen activation in the pancreas is known to be a trigger reaction in the development of pancreatitis. Nafamostat blocks the activation of trypsinogen to trypsin and the inflammatory cascade that follows. Nafamostat may also decrease epithelial sodium channel (ENaC) activity and increase mucus clearance in the airways. ENaC activity is increased in cystic fibrosis. In addition, nafamostat 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.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Nafamostat.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(6-carbamimidoylnaphthalen-2-yl) 4-(diaminomethylideneamino)benzoate
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 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)
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

MQQNFDZXWVTQEH-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C1=CC(=CC=C1C(=O)OC2=CC3=C(C=C2)C=C(C=C3)C(=N)N)N=C(N)N
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C19H17N5O2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 UNII

2.3.3 ChEBI ID

2.3.4 ChEMBL ID

2.3.5 DrugBank ID

2.3.6 DSSTox Substance ID

2.3.7 HMDB ID

2.3.8 KEGG ID

2.3.9 Metabolomics Workbench ID

2.3.10 NCI Thesaurus Code

2.3.11 Nikkaji Number

2.3.12 PharmGKB ID

2.3.13 Pharos Ligand ID

2.3.14 Wikidata

2.3.15 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 6'-amidino-2-naphthyl 4-guanidinobenzoate
  • 6'-amidino-2-naphthyl 4-guanidinobenzoate, dimethanesulfonate
  • Benzoic acid, 4-((aminoiminomethyl)amino)-, 6-(aminoiminomethyl)-2-naphthalenyl ester
  • Benzoic acid, 4-((aminoiminomethyl)amino)-, 6-(aminoiminomethyl)-2-naphthalenyl ester, dihydrochloride
  • Benzoic acid, 4-((aminoiminomethyl)amino)-, 6-(aminoiminomethyl)-2-naphthalenyl ester, dimethanesulfonate
  • CKD-314
  • CKD314
  • FUT 175
  • FUT-175
  • nafamostat
  • nafamostat dihydrochloride
  • nafamostat mesilate
  • nafamostat mesylate
  • nafamstat mesilate
  • Ronastat

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
347.4 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
2
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
347.13822480 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
347.13822480 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
141 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
26
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
552
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Chemical Classes

3.2.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
Pharmaceutical
S120 | DUSTCT2024 | Substances from Second NORMAN Collaborative Dust Trial | DOI:10.5281/zenodo.13835254

5 Chemical Vendors

6 Drug and Medication Information

6.1 Drug 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.

6.2 Clinical Trials

6.2.1 ClinicalTrials.gov

6.2.2 EU Clinical Trials Register

6.2.3 NIPH Clinical Trials Search of Japan

7 Pharmacology and Biochemistry

7.1 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.

7.2 MeSH Pharmacological Classification

Anticoagulants
Agents that prevent BLOOD CLOTTING. (See all compounds classified as Anticoagulants.)
Serine Proteinase Inhibitors
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES. (See all compounds classified as Serine Proteinase Inhibitors.)
Trypsin Inhibitors
Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds. (See all compounds classified as Trypsin Inhibitors.)
Anti-Inflammatory Agents, Non-Steroidal
Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)
Protease Inhibitors
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). (See all compounds classified as Protease Inhibitors.)
Complement Inactivating Agents
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. (See all compounds classified as Complement Inactivating Agents.)

7.3 Absorption, Distribution and Excretion

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.

7.4 Metabolism / Metabolites

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.

7.5 Biological Half-Life

Approximately 8 minutes

7.6 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). 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.

8 Associated Disorders and Diseases

9 Literature

9.1 Consolidated References

9.2 NLM Curated PubMed Citations

9.3 Springer Nature References

9.4 Thieme References

9.5 Chemical Co-Occurrences in Literature

9.6 Chemical-Gene Co-Occurrences in Literature

9.7 Chemical-Disease Co-Occurrences in Literature

10 Patents

10.1 Depositor-Supplied Patent Identifiers

10.2 WIPO PATENTSCOPE

10.3 Chemical Co-Occurrences in Patents

10.4 Chemical-Disease Co-Occurrences in Patents

10.5 Chemical-Gene Co-Occurrences in Patents

11 Interactions and Pathways

11.1 Protein Bound 3D Structures

11.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

11.2 Chemical-Target Interactions

11.3 Drug-Drug Interactions

11.4 Drug-Food Interactions

Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

11.5 Pathways

12 Biological Test Results

12.1 BioAssay Results

13 Classification

13.1 MeSH Tree

13.2 NCI Thesaurus Tree

13.3 ChEBI Ontology

13.4 KEGG: Drug Groups

13.5 ChemIDplus

13.6 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

13.7 ChEMBL Target Tree

13.8 NORMAN Suspect List Exchange Classification

13.9 EPA DSSTox Classification

13.10 MolGenie Organic Chemistry Ontology

14 Information Sources

  1. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  6. ChEBI
  7. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  8. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  9. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  10. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  11. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  12. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  13. Therapeutic Target Database (TTD)
  14. EU Clinical Trials Register
  15. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  16. Japan Chemical Substance Dictionary (Nikkaji)
  17. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
  18. Metabolomics Workbench
  19. NIPH Clinical Trials Search of Japan
  20. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Nafamostat
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  21. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  22. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  23. Protein Data Bank in Europe (PDBe)
  24. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  25. Springer Nature
  26. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  27. Wikidata
  28. Wikipedia
  29. PubChem
  30. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
    Serine Proteinase Inhibitors
    https://www.ncbi.nlm.nih.gov/mesh/68015842
    Anti-Inflammatory Agents, Non-Steroidal
    https://www.ncbi.nlm.nih.gov/mesh/68000894
    Complement Inactivating Agents
    https://www.ncbi.nlm.nih.gov/mesh/68051056
  31. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  32. PATENTSCOPE (WIPO)
CONTENTS