TM5441

Names

[ CAS No. ]:
1190221-43-2

[ Name ]:
TM5441

[Synonym ]:
5-chloro-2-([(2-([3-(furan-3-yl)phenyl]amino)-2-oxoehtoxy)acetyl]amino)benzoic acid

Biological Activity

[Description]:

TM5441 is a plasminogen activator inhibitor-1 (PAI-1); inhibits several tumor cell lines with IC50 values between 9.7 and 60.3 μM.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> PAI-1

Research Areas >> Cancer

[Target]

IC50: 9.7 and 60.3 μM (Tumor cell lines)[1]

[In Vitro]

TM5441 dose-dependently decreases HT1080, HCT116, Daoy, MDA-MB-231 and Jurkat cells with an IC50 ranging between 9.7 and 60.3 μM. TM5441 decreases tumor cell viability in part through diminished proliferation. TM5441 increases caspase 3/7 activity for both HT1080 and HCT116 cells in a dose dependant manner. TM5441is a potent stimulators of intrinsic apoptosis in tumor cells. 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].

[In Vivo]

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 effectively inhibits albuminuria, mesangial expansion, ECM accumulation, and macrophage infiltration in diabetic kidneys[2].

[Cell Assay]

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].

[Animal admin]

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].

[References]

[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.

[Related Small Molecules]

Tiplaxtinin | TM 5275 sodium salt | Loureirin B

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₁H₁₇ClN₂O₆

[ Molecular Weight ]:
428.829

[ Storage condition ]:
-20℃