TM5441 is an orally bioavailable inhibitor of plasminogen activator inhibitor-1 (PAI-1), has IC₅₀ values between 13.9 and 51.1 μM and induces intrinsic apoptosis in several human cancer cell lines. TM5441 attenuates Nω-nitro-l-arginine methyl ester-induced cardiac hypertension and vascular senescence^[1][2].

IC50: 13.9~51.1 μM (Tumor cell lines)^[1]

TM5441 dose-dependently decreases HT1080, HCT116, Daoy, MDA-MB-231 and Jurkat cells with an IC₅₀ ranging between 13.9 and 51.1 μM^[1].
TM5441 increases caspase 3/7 activity for both HT1080 and HCT116 cells in a dose dependant manner. TM5441 increases apoptosis in HT1080 and HCT116 cells^[1].
TM5441 induces mitochondrial depolarization^[1].
In mouse proximal tubular epithelial cells, TM5441 effectively inhibits PAI-1-induced mRNA expression of fibrosis and inflammation markers and also reverses PAI-1-induced inhibition of plasmin activity^[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.

Oral administration of TM5441 (20 mg/kg daily) to HT1080 and HCT116 xenotransplanted mice increases tumor cell apoptosis and has a significant disruptive effect on the tumor vasculature that is associated with a decrease in tumor growth and an increase in survival. The average peak plasma concentration is 11.4 μM one hour after oral administration and undetectable levels 23 hours after administration^[1].
TM5441 attenuates Nω-nitro-l-arginine methyl ester-induced cardiac hypertension and vascular senescence, prolongs lifespan in klotho null mice and elicits anti-tumorigenic and anti-angiogenic activities in cancer^[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.

428.82

C₂₁H₁₇ClN₂O₆

1190221-43-2

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 300 mg/mL (699.59 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。

In Vivo:

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    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.83 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.83 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.83 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.83 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Placencio VR, et al. Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti-Angiogenic Activity. PLoS One. 2015 Jul 24;10(7):e0133786.

  [2]. Jeong BY, et al. Novel Plasminogen Activator Inhibitor-1 Inhibitors Prevent Diabetic Kidney Injury in a Mouse Model. PLoS One. 2016 Jun 3;11(6):e0157012.

HT1080, HCT116, Daoy, MDA-MB-231 and Jurkat cells are treated with 0-100 μM TM5441 for 48 hours at 37°C. Cell viability is measured by MTT assay^[1].

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.

Mice: TM5275 at 50 mg/kg/day and TM5441 at 10 mg/kg/day were orally administered in control and diabetic mice for 16 weeks. Mice were monitored at least once a day. At the end, blood is collected for measurement of plasma glucose and creatinine, urine for protein measurement, and kidneys for immunohistochemical analysis^[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.

• [1]. Placencio VR, et al. Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti-Angiogenic Activity. PLoS One. 2015 Jul 24;10(7):e0133786.

  [2]. Jeong BY, et al. Novel Plasminogen Activator Inhibitor-1 Inhibitors Prevent Diabetic Kidney Injury in a Mouse Model. PLoS One. 2016 Jun 3;11(6):e0157012.