| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
Patamostat targets serine proteases including trypsin, plasmin, plasma kallikrein, and to a lesser extent thrombin and factor Xa. Its primary mechanism involves reversible competitive inhibition of the active site of these enzymes, preventing proteolysis of substrates such as fibrinogen, collagen, and other extracellular matrix proteins. This inhibition helps to reduce inflammation and tissue damage.
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| ln Vitro |
A standard chromogenic substrate assay is used to evaluate Patamostat activity. Purified trypsin or plasmin (0.1-1 ug/mL) is incubated with varying concentrations of Patamostat (0.1-1000 nM) in Tris-HCl buffer (pH 7.4-8.0) at 37degC. After 5-10 min, a chromogenic substrate (e.g., N-benzoyl-L-arginine p-nitroanilide, BApNA) is added. The release of p-nitroaniline is monitored continuously at 405 nm. IC50 values are calculated as the concentration required for 50% inhibition of enzyme activity.
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| ln Vivo |
Pamostat (intravenous infusion) decreases mortality following induced pancreatitis in a dose-dependent manner, whether administered to rats at 0.03-0.3 mg/kg or to rabbits at 0.3-3.0 mg/kg in [1]. Dogs with pancreatitis see a decrease in serum trypsin and lipase activity when their intravenous infusion of Pamestat (1.0–3.0 mg/kg) is administered [1]. When administered continuously, patamostat (2 mg/kg/h) improves almost all measures in male Wistar rats, including plasma endotoxin and serum FDP levels, as well as mortality, serum and ascitic fluid amylase levels, and lysosomal enzyme profiles [2].
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| Cell Assay |
For cellular assays, primary human fibroblasts or endothelial cells are seeded in 96-well plates and treated with Patamostat (0.1-100 uM) for 1-24 h. Plasminogen activator (uPA or tPA) activity is measured using a chromogenic substrate in cell lysates or conditioned medium. Cell viability is assessed by MTT or LDH release assays. For protease activity assays, conditioned medium is collected from cells (e.g., cancer cells known to secrete uPA), incubated with Patamostat, and then mixed with the chromogenic substrate S-2444 (pyroGlu-Gly-Arg-pNA). Absorbance is measured to determine inhibition of uPA activity. For cellular anti-inflammatory assays, LPS-stimulated macrophages are treated with Patamostat, and TNF-alpha and IL-6 levels are measured by ELISA.
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| Animal Protocol |
Animal/Disease Models: Male Wistar rats, weighing approximately 350 g [2]
Doses: 2 mg/kg Route of Administration: Continuous infusion every hour for 1 hour Experimental Results: Dramatically improved survival rate. A typical in vivo experiment involves the induction of pancreatitis in mice or rats by administration of caerulein (50 ug/kg, 6-12 hourly doses). Patamostat is administered intravenously or intraperitoneally at 0.1-10 mg/kg prior to and/or during caerulein treatment. Efficacy endpoints include serum amylase and lipase levels, pancreatic edema (wet weight), histological assessment of pancreatic necrosis and inflammation, and measurement of pro-inflammatory cytokines (e.g., IL-6, TNF-alpha) in pancreatic tissue. In models of disseminated intravascular coagulation (DIC), Patamostat is administered to rats after induction by endotoxin or thromboplastin; fibrinogen levels, platelet counts, and bleeding time are evaluated. |
| ADME/Pharmacokinetics |
Patamostat exhibits favorable pharmacokinetic properties as a small-molecule serine protease inhibitor. In preclinical animal models (rats, dogs), it shows rapid distribution and moderate half-life (t1/2 approx. 0.5-2 h). Clearance is primarily via renal excretion. Its short half-life may require continuous intravenous infusion for sustained efficacy. Plasma protein binding is moderate (approximately 60-80%).
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| Toxicity/Toxicokinetics |
In preclinical toxicology studies, Patamostat was generally well-tolerated at therapeutic doses. Potential adverse effects include prolonged bleeding time due to inhibition of plasmin and other proteases involved in hemostasis. No significant target-independent organ toxicity was observed at doses up to 10-fold the therapeutic range. High-dose administration may cause gastrointestinal disturbances. Comprehensive safety data were generated for regulatory submission but are not publicly available.
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| References |
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| Additional Infomation |
Patamostat was developed by Eisai Co., Ltd. and advanced to clinical trials for the treatment of acute pancreatitis and disseminated intravascular coagulation (DIC). It completed Phase 2/3 studies in Japan and other Asian countries. However, the compound did not receive marketing approval, and further development was discontinued. It remains available as a research-grade compound for laboratory use to study serine protease inhibition. Its chemical structure is protected by patents expiring many years ago.
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| Molecular Formula |
C₂₀H₂₀N₄O₄S
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|---|---|
| Molecular Weight |
412.46
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| Exact Mass |
412.121
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| CAS # |
114568-26-2
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| Related CAS # |
Patamostat mesylate;114568-32-0
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| PubChem CID |
65921
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| Appearance |
White to off-white solid powder
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| Density |
1.41g/cm3
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| Boiling Point |
701.5ºC at 760mmHg
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| Flash Point |
378.1ºC
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| Vapour Pressure |
1.58E-19mmHg at 25°C
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| Index of Refraction |
1.678
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| LogP |
3.263
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
29
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| Complexity |
620
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ILRQPCQIFIURTG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H20N4O4S/c21-20(22)23-14-3-1-13(2-4-14)19(27)28-15-5-7-16(8-6-15)29-12-11-24-17(25)9-10-18(24)26/h1-8H,9-12H2,(H4,21,22,23)
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| Chemical Name |
Benzoic acid, 4-((aminoiminomethyl)amino)-, 4-((2-(2,5-dioxo-1-pyrrolidinyl)ethyl)thio)phenyl ester
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| Synonyms |
PatamostatE-3123 E 3123 E3123
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~242.45 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4245 mL | 12.1224 mL | 24.2448 mL | |
| 5 mM | 0.4849 mL | 2.4245 mL | 4.8490 mL | |
| 10 mM | 0.2424 mL | 1.2122 mL | 2.4245 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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