Nafamostat

Last updated
Nafamostat mesylate
Nafamostat.svg
Clinical data
AHFS/Drugs.com International Drug Names
Routes of
administration 		IV
ATC code
  • none
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
  • 6-[amino(imino)methyl]-2-naphthyl 4-{[amino(imino)methyl]amino}benzoate
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula C19H17N5O2
Molar mass 347.378 g·mol−1
3D model (JSmol)
  • N=C(N)c1ccc2cc(OC(=O)c3ccc(N=C(N)N)cc3)ccc2c1
  • 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) X mark.svgN
  • Key:MQQNFDZXWVTQEH-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Nafamostatmesylate (INN), a synthetic serine protease inhibitor, is a short-acting anticoagulant, [1] and it is also used for the treatment of pancreatitis. It also has some potential antiviral and anti-cancer properties. [2] Nafamostat is a fast-acting proteolytic inhibitor and used during hemodialysis to prevent the proteolysis of fibrinogen into fibrin. [3] 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. [4] [5]

It inhibits a large number of Lys/Arg specific serine proteinases, and is also a tryptase inhibitor, which is implicated in leaking blood vessels which is symptomatic of dengue hemorrhagic fever and of end-stage dengue shock syndrome. [6] It is available in a generic form already used for the treatment of certain bleeding complications in some countries, there are risks of severe complications such as: agranulocytosis, hyperkalemia, and anaphylaxis which must be weighed in non-emergency care. [7] In some countries, it used as a treatment for pancreatitis and pancreatic cancer.[ citation needed ]

This drug has been identified as a potential therapy for COVID-19, [8] [9] with clinical trials in Japan possibly set to begin in March 2020. [10] With evidence that nafamostat is a potent anti-viral inhibitor in lung cells, a second round of clinical trials in Korea has begun with 10 hospitals participating. [11] Multiple Phase 2/3 [12] [13] [14] and Phase 3 [15] [16] clinical trials for COVID-19 in different countries are ongoing.

It has also been reported to target tubulin, favorizing its polymerization. [17]


References

  1. ↑ Al-Horani RA, Desai UR (November 2014). "Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders". Medicinal Research Reviews. 34 (6): 1168–1216. doi:10.1002/med.21315. PMC   8788159 . PMID   24659483. S2CID   22631056.
  2. ↑ Chen X, Xu Z, Zeng S, Wang X, Liu W, Qian L, et al. (2019). "The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications". Frontiers in Oncology. 9: 852. doi: 10.3389/fonc.2019.00852 . PMC   6733886 . PMID   31552177.
  3. ↑ Sadahiro T, Yuzawa H, Kimura T, Oguchi M, Morito T, Mizushima S, Hirose Y (2018). "Current Practices in Acute Blood Purification Therapy in Japan and Topics for Further Study". Contributions to Nephrology. 196: 209–214. doi:10.1159/000485724. ISBN   978-3-318-06297-7. PMID   30041229.
  4. ↑ Ramjee MK, Henderson IM, McLoughlin SB, Padova A (June 2000). "The kinetic and structural characterization of the reaction of nafamostat with bovine pancreatic trypsin". Thrombosis Research. 98 (6): 559–569. doi:10.1016/s0049-3848(00)00206-1. PMID   10899355.
  5. ↑ Ramjee MK, Patel S (July 2017). "Continuous-flow injection microfluidic thrombin assays: The effect of binding kinetics on observed enzyme inhibition". Analytical Biochemistry. 528: 38–46. doi:10.1016/j.ab.2017.04.016. PMID   28456636.
  6. ↑ Rathore AP, Mantri CK, Aman SA, Syenina A, Ooi J, Jagaraj CJ, et al. (July 2019). "Dengue virus-elicited tryptase induces endothelial permeability and shock". The Journal of Clinical Investigation. 129 (10): 4180–4193. doi:10.1172/JCI128426. PMC   6763290 . PMID   31265436.
  7. ↑ "Nafamostat". PubChem. U.S. National Library of Medicine. Retrieved 17 June 2020.
  8. ↑ Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. (March 2020). "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro". Cell Research. 30 (3): 269–271. doi:10.1038/s41422-020-0282-0. PMC   7054408 . PMID   32020029.
  9. ↑ Huang J, Ma Q, Su Z, Cheng X (October 2024). "Advancements in the Development of Anti-SARS-CoV-2 Therapeutics". International Journal of Molecular Sciences. 25 (19) 10820. doi: 10.3390/ijms251910820 . PMC   11477007 . PMID   39409149.
  10. ↑ "Japanese researchers to test blood thinner for coronavirus treatment". The Japan Times Online. 19 March 2020. ISSN   0447-5763 . Retrieved 24 March 2020.
  11. ↑ "Korean researchers find drug that is more effective in treating COVID-19 than remdesivir". Pharmafile. 15 May 2020. Retrieved 2020-06-17.
  12. ↑ Clinical trial number NCT04473053 for "Rapid Experimental Medicine for COVID-19" at ClinicalTrials.gov
  13. ↑ Clinical trial number NCT04352400 for "Efficacy of Nafamostat in Covid-19 Patients (RACONA Study)" at ClinicalTrials.gov
  14. ↑ Clinical trial number NCT04418128 for "Clinical Efficacy of Nafamostat Mesylate for COVID-19 Pneumonia" at ClinicalTrials.gov
  15. ↑ Clinical trial number NCT04483960 for "Australasian COVID-19 Trial (ASCOT) ADAptive Platform Trial" at ClinicalTrials.gov
  16. ↑ Clinical trial number NCT04390594 for "Efficacy and Safety Evaluation of Treatment Regimens in Adult COVID-19 Patients in Senegal" at ClinicalTrials.gov
  17. ↑ Baksheeva VE, La Rocca R, Allegro D, Derviaux C, Pasquier E, Roche P, Morelli X, Devred F, Golovin AV, Tsvetkov PO (2025). "NanoDSF Screening for Anti-tubulin Agents Uncovers New Structure–Activity Insights". Journal of Medicinal Chemistry. doi:10.1021/acs.jmedchem.5c01008.
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