Nafamostat mesylate (FUT-175), a synthetic serine protease inhibitor, functions as an anticoagulant and exhibits both anticancer and antiviral effects. It is known to induce apoptosis by up-regulating the expression of tumor necrosis factor receptor-1 (TNFR1), and it is also used in studies related to the pathological thickening of arterial walls[1].[2].
体内研究
In an in vivo setting, Nafamostat mesylate administered at a dose of 10 mg/kg through intraperitoneal injection once daily for 18 days demonstrates favorable antiviral properties against Zika virus (ZIKV) infection in A129 mice[3].
Additionally, when given at dosages between 0.5 and 2.0 mg/mL (dissolved in saline) via intraperitoneal injection daily for seven consecutive days, it effectively inhibits neointimal formation after balloon injury of the rat carotid wall[4].
体外研究
In laboratory studies, Nafamostat mesylate at concentrations ranging from 10 to 80 μg/mL over durations of 3 to 48 hours inhibits NF-κB activity by blocking the phosphorylation of IκBα in MDAPanc-28 cells[1].
When applied at 80 μg/mL for 24 to 48 hours, it induces apoptosis in these cells by up-regulating TNFR1[1].
Furthermore, Nafamostat mesylate has shown effectiveness in reducing the invasiveness of Panc-1 cells at concentrations from 0.1 to 10 μM over a 24-hour period[2].
Nafamostat Mesylate/甲磺酸萘莫司他 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human bronchial epithelial cells
25 µM
1 hour
Nafamostat significantly inhibited SARS-CoV-2 and MERS-CoV infection in human airway epithelial cells, suggesting it blocks viral entry by inhibiting cell surface serine proteases such as TMPRSS2.
mBio. 2021 Aug 31;12(4):e0097021.
Calu-3 2B4 cells
2.2 nM (IC50)
1 hour
Nafamostat showed greater potency than camostat in inhibiting SARS-CoV-2 and MERS-CoV infection in Calu-3 2B4 cells.
mBio. 2021 Aug 31;12(4):e0097021.
Bone marrow-derived macrophages
50 µM
6 hours
Inhibition of intracellular trypsin activity in macrophages, preventing NF-κB nuclear translocation
Gastroenterology. 2018 Feb;154(3):704-718.e10.
Human tracheal epithelial cells (HTE)
10 μg/ml
72 hours
Pretreatment with nafamostat significantly reduced the titers of the pandemic and seasonal influenza viruses in HTE cells and decreased the secretion of inflammatory cytokines (e.g., IL-6 and TNF-α) in the supernatants of cells infected with the pandemic influenza virus.
J Med Virol. 2021 Jun;93(6):3484-3495.
Human nasal epithelial cells (HNE)
10 μg/ml
72 hours
Pretreatment with nafamostat significantly reduced the titers of the pandemic and seasonal influenza viruses in HNE cells and decreased the secretion of inflammatory cytokines (e.g., IL-6 and TNF-α) in the supernatants of cells infected with the pandemic influenza virus.
J Med Virol. 2021 Jun;93(6):3484-3495.
Rat hippocampal CA1 pyramidal neurons
0.20 ± 0.04 µM (IC50)
To study the inhibitory effect of Nafamostat on NMDA receptors, the results showed an IC50 of 0.20 ± 0.04 µM, indicating a strong inhibitory effect.
Int J Mol Sci. 2023 Oct 27;24(21):15685.
Nafamostat Mesylate/甲磺酸萘莫司他 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Wistar rats
Spinal cord injury model
Intraperitoneal injection
10 mg/kg
Twice daily for 7 days
Nafamostat mesilate treatment significantly improved locomotion recovery after spinal cord injury, reduced inflammation and apoptosis, and promoted tissue preservation.
CNS Neurosci Ther. 2018 May;24(5):429-438
Rats
Sprague-Dawley rats
Intravenous and intratracheal administration
10 mg/kg
Single dose
Evaluate the pharmacokinetics and lung distribution of Nafamostat under different administration routes, finding that intratracheal administration had higher drug delivery and longer residual time in the lung lumen and tissue
Pharmaceutics. 2021 Sep 19;13(9):1519
Rats
Spinal cord injury model
Intraperitoneal injection
10 mg/kg/day
Twice a day until 3 dpi or the endpoints of experiments
To evaluate the optimal administration time window of Nafamostat after spinal cord injury and its impact on functional recovery. The results showed that Nafamostat administration within 2-12 hours post-injury significantly improved motor function and nerve conduction, with the best effects observed at 8 and 12 hours post-injury.
J Neuroinflammation. 2022 Jul 16;19(1):189
BALB/c mice
Asthma model
Intraperitoneal injection
20 mg/kg
30 minutes before each HDM challenge, for 6 weeks
To evaluate the effects of Nafamostat on airway hyperreactivity, inflammatory parameters, and gene expression in a mouse model of asthma. Results showed that Nafamostat significantly suppressed airway hyperreactivity in HDM-sensitized mice, reduced infiltration of eosinophils and lymphocytes into the airways, and lowered levels of pro-inflammatory compounds in the airway lumen. Additionally, Nafamostat dampened goblet cell hyperplasia and smooth muscle layer thickening in the lungs of HDM-sensitized animals.
Front Immunol. 2023 Apr 21;14:1136780
Mice
K18-hACE2 transgenic mice
Subcutaneous injection
20 mg/kg, 60 mg/kg, 100 mg/kg
Once daily for 5 days
To evaluate the protective efficacy of MDB-601a-NM against SARS-CoV-2 infection, results showed that 60 mg/kg and 100 mg/kg dose groups performed better in terms of weight loss and survival rate, and no viral replication was detected in brain tissue.
Int J Mol Sci. 2023 May 31;24(11):9579
Mice
Ad5-hACE2 transduced mice and K18-hACE2 transgenic mice
Intranasal administration
3 mg/kg
Single dose, 2 hours before infection
Nafamostat significantly reduced SARS-CoV-2-induced weight loss, viral load, and mortality in Ad5-hACE2 transduced mice and K18-hACE2 transgenic mice, particularly when administered before infection.
mBio. 2021 Aug 31;12(4):e0097021.
CD-1 mice
TLR7/8 agonist R848-induced virus-like illness model
Intravenous injection
3 mg/kg
Single injection, duration of 6 hours
To evaluate the anti-inflammatory effects of Nafamostat in a TLR7/8 agonist R848-induced virus-like illness model. Results showed that Nafamostat suppressed the hepatic inflammatory response, significantly reducing TNF and IFN-γ expression, but had no effect on lung or brain cytokine production. Additionally, Nafamostat restored the R848-induced depletion of circulating leukocytes.
J Neuroinflammation. 2022 Jan 6;19(1):8
BALB/c mice
Influenza A virus infection model
Intraperitoneal injection
30 mg/kg/day
Once daily for 14 days
Nafamostat reduced the levels of the pandemic influenza virus in mouse lungs but did not improve survival rate or body weight reduction after infection.
Korea, Republic of
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National Health Insurance Corporation Ilsan Hospital
Recruiting
Koyang, Korea, Republic of
Contact: Tae Ik Chang, MD 82-31-900-0246 tichang@hanmail.net
Seoul National University Bundang Hospital
Recruiting
Seongnam, Korea, Republic of
Contact: Sejoong Kim, MD, PhD 82-11-9196-5245 imsejoong@hanmail.net
Seoul National University Boramae Medical Center
Recruiting
Seoul, Korea, Republic of
Contact: Jung Pyo Lee, MD, PhD 82-2-870-2261 kjwa1@medimail.co.kr
Seoul National University Hospital
Recruiting
Seoul, Korea, Republic of
Contact: Su Mi Lee 82-2-2072-1705 promise131@hanmail.net 收起 <<
Korea, Republic of
... 展开 >>
National Health Insurance Corporation Ilsan Hospital
Recruiting
Koyang, Korea, Republic of
Contact: Tae Ik Chang, MD 82-31-900-0246 tichang@hanmail.net
Seoul National University Bundang Hospital
Recruiting
Seongnam, Korea, Republic of
Contact: Sejoong Kim, MD, PhD 82-11-9196-5245 imsejoong@hanmail.net
Seoul National University Boramae Medical Center
Recruiting
Seoul, Korea, Republic of
Contact: Jung Pyo Lee, MD, PhD 82-2-870-2261 kjwa1@medimail.co.kr
Seoul National University Hospital
Recruiting
Seoul, Korea, Republic of
Contact: Su Mi Lee 82-2-2072-1705 promise131@hanmail.net 收起 <<
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