Biological Activity
TM5441 is a plasminogen activator inhibitor-1 (PAI-1); inhibits several tumor cell lines with IC50 values between 9.7 and 60.3 μM.
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].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.