TM5441

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 & Target: IC50: 13.9~51.1 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 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]. 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 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].