Upamostat (WX-671) is a serine protease inhibitor. Upamostat is the orally available prodrug of the WX-UK1, which is a urokinase plasminogen activator (uPA) inhibitor.

Serine protease, uPA^[1]

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

629.81

C₃₂H₄₇N₅O₆S

590368-25-5

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 250 mg/mL (396.95 mM)

* “≥” means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (3.30 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (3.30 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [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.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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.