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| 25mg |
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| Targets |
Serine protease, uPA[1]
Upamostat targets urokinase-type plasminogen activator (uPA), a serine protease involved in the uPA system that plays a major role in tumor invasion and metastasis. By inhibiting uPA, Upamostat blocks the conversion of plasminogen to plasmin, interfering with extracellular matrix degradation. The compound is the oral prodrug of the active metabolite WX-UK1. Its mechanism involves inhibition of tumor cell invasion, migration, and metastasis. |
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| ln Vitro |
Upamostat is a urokinase plasminogen activator (uPA) inhibitor. Upamostat is an oral prodrug for the active metabolite WX-UK1, a novel uPA inhibitor [1]. Upamostat inhibits the urokinase-type plasminogen activator (uPA) system, which is involved in tumor invasion and metastasis. Upamostat is the orally available amidoxime (i.e., hydroxyamidine) prodrug of the pharmacologically active form, WX-UK1[2].
In vitro, Upamostat is a serine protease inhibitor and uPA inhibitor. It blocks uPA activity, inhibiting the conversion of plasminogen to plasmin. The compound interferes with extracellular matrix degradation associated with tumor cell invasion and metastasis. Its uPA inhibitory activity has been characterized in various enzyme-based and cell-based assays. Upamostat is the oral prodrug of the active metabolite WX-UK1. |
| ln Vivo |
Rat Upamostat (Mesupron) pharmacokinetics are assessed using the validation method. Five rats get a single intravenous injection of 2 mg/kg of Upamostat, and the mean plasma concentrations of the drug are determined. The material has a terminal half-life of 0.5 hours, a monophasic decay pattern, a 2.0 L/kg volume of distribution, and a clearance of roughly 2.7 L/h/kg[3].
In vivo, Upamostat is an orally active serine protease inhibitor that inhibits uPA, blocking plasminogen activation and interfering with extracellular matrix degradation. It is used in research for metastatic breast cancer and locally advanced pancreatic cancer. The compound's oral bioavailability enables convenient administration in preclinical studies. Its anti-invasive and anti-metastatic effects have been demonstrated in animal models of cancer. Further in vivo studies are ongoing to fully characterize its therapeutic potential. |
| Enzyme Assay |
In vitro enzyme assays for Upamostat involve measuring uPA inhibition. uPA activity is assessed using fluorogenic or chromogenic substrates. The compound is added at varying concentrations, and IC50 values are calculated from dose-response curves. For selectivity studies, inhibition of other serine proteases is assessed. Plasminogen activation assays are performed to confirm the mechanism of action. Assays are performed in appropriate buffer systems with positive controls such as known uPA inhibitors.
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| Cell Assay |
In vitro cell-based assays for Upamostat are conducted in cancer cell lines. Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with the compound at varying concentrations. Cell viability is assessed by MTT or CCK-8 assays. Invasion and migration are assessed using Transwell or wound healing assays. uPA activity in cell lysates is measured. Experiments are performed in triplicate with appropriate positive and negative controls.
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| Animal Protocol |
Rats[3] Five 9-week old Sprague-Dawley rats are administered a single intravenous injection of 2 mg/kg of Upamostat. Upamostat is dissolved in a mixture of normal saline, dimethylacetamide, polyethylene glycol 400 and DMSO (3:3:3:1). Blood samples (0.15 mL) are taken serially for up to 10 h after drug administration and collected in heparinized centrifuge tubes. After centrifugation at 13,200 rpm for 10 min, the plasma samples are analyzed[3]. |
| ADME/Pharmacokinetics |
Upamostat (MW 629.81 g/mol, C32H47N5O6S) is a serine protease inhibitor and orally active prodrug of WX-UK1. It is also known as WX-671. The compound is soluble in DMSO and other organic solvents. It is stable under recommended storage conditions. Upamostat is a uPA inhibitor used in cancer research. Pharmacokinetic parameters such as half-life, bioavailability, and tissue distribution would be determined in species-specific studies.
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| Toxicity/Toxicokinetics |
Upamostat is generally well-tolerated in preclinical studies. The compound is a serine protease inhibitor with established safety profiles. Its uPA inhibitory and anti-metastatic effects have been demonstrated with acceptable safety profiles. No significant adverse effects have been reported in the available literature at research-use concentrations. The compound is intended for research use only. Standard safety precautions should be followed when handling. Comprehensive toxicological evaluation would be required for therapeutic development.
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| References |
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| Additional Infomation |
Upamostat has been used in clinical trials for the treatment of pancreatic cancer. Upamostat is a highly bioavailable 3-amidinylphenylalanine derivative, belonging to the second-generation serine protease inhibitor prodrug family. It targets the human urokinase-type plasminogen activator (uPA) system and possesses potential antitumor and antimetastatic activities. After oral administration, Upamostat is converted into the active compound Nα-(2,4,6-triisopropylbenzenesulfonyl)-3-amidinyl-(L)-phenylalanine-4-ethoxycarbonylpiperazine (WX-UK1), which inhibits various serine proteases, especially uPA; inhibition of uPA may lead to the inhibition of tumor growth and metastasis. uPA is a serine protease involved in the degradation of the extracellular matrix and the migration and proliferation of tumor cells.
Upamostat (WX-671) is a serine protease inhibitor and orally active prodrug of WX-UK1 that functions as a urokinase-type plasminogen activator (uPA) inhibitor. It blocks uPA activity, inhibiting plasminogen activation and extracellular matrix degradation associated with tumor invasion and metastasis. The compound is used in research for metastatic breast cancer and locally advanced pancreatic cancer. Its molecular formula is C32H47N5O6S with a molecular weight of 629.81 g/mol. All applications are limited to non-human research use. |
| Molecular Formula |
C₃₂H₄₇N₅O₆S
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|---|---|
| Molecular Weight |
629.81
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| Exact Mass |
629.325
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| CAS # |
590368-25-5
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| Related CAS # |
590368-25-5
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| PubChem CID |
9852201
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| Appearance |
White to off-white solid powder
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| Density |
1.25
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| LogP |
6.298
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
44
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| Complexity |
1070
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCOC(=O)N1CCN(CC1)C(=O)[C@H](CC2=CC(=CC=C2)/C(=N/O)/N)NS(=O)(=O)C3=C(C=C(C=C3C(C)C)C(C)C)C(C)C
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| InChi Key |
HUASEDVYRABWCV-NDEPHWFRSA-N
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| InChi Code |
InChI=1S/C32H47N5O6S/c1-8-43-32(39)37-14-12-36(13-15-37)31(38)28(17-23-10-9-11-24(16-23)30(33)34-40)35-44(41,42)29-26(21(4)5)18-25(20(2)3)19-27(29)22(6)7/h9-11,16,18-22,28,35,40H,8,12-15,17H2,1-7H3,(H2,33,34)/t28-/m0/s1
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| Chemical Name |
ethyl 4-[(2S)-3-[3-[(Z)-N'-hydroxycarbamimidoyl]phenyl]-2-[[2,4,6-tri(propan-2-yl)phenyl]sulfonylamino]propanoyl]piperazine-1-carboxylate
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| Synonyms |
WX-671WX 671Mesupron WX671
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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 |
| 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 : ≥ 250 mg/mL (~396.95 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5878 mL | 7.9389 mL | 15.8778 mL | |
| 5 mM | 0.3176 mL | 1.5878 mL | 3.1756 mL | |
| 10 mM | 0.1588 mL | 0.7939 mL | 1.5878 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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