| Description |
Upamostat is a serine protease inhibitor. Upamostat is the orally available prodrug of the WX-UK1, which is a urokinase plasminogen activator (uPA) inhibitor.
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| Related Catalog |
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| Target |
Serine protease, uPA[1]
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| In Vitro |
Upamostat is the urokinase plasminogen activator (uPA) inhibitor. Upamostat is the oral pro-drug of the active metabolite WX-UK1, a novel uPA inhibitor[1]. Upamostat inhibits the urokinase-type plasminogen activator (uPA) system, which plays a major role in tumor invasion and metastasis. Upamostat is the orally available amidoxime- (i.e. hydroxyamidine-) prodrug of the pharmacologically active form, WX-UK1[2].
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| In Vivo |
The validated method is used to evaluate the pharmacokinetics of Upamostat (Mesupron) in rats. The mean plasma concentrations of Upamostat after a single intravenous injection of 2 mg/kg in five rats are measured. The substance decays in a mono-phasic pattern with a terminal half-life of 0.5 h; its volume of distribution is 2.0 L/kg, and clearance is about 2.7 L/h/kg[3].
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| Animal Admin |
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].
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| References |
[1]. Heinemann V, et al. Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer. Br J Cancer. 2013 Mar 5;108(4):766-70. [2]. Froriep D, et al. Activation of the anti-cancer agent upamostat by the mARC enzyme system. Xenobiotica. 2013 Sep;43(9):780-4. [3]. Park C, et al. HPLC-MS/MS analysis of mesupron and its application to a pharmacokinetic study in rats. J Pharm Biomed Anal. 2018 Feb 20;150:39-42.
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