TM-5441

Description: TM-5441 (EBP 883 and BMS-790052) is a novel orally active and potent small molecule inhibitor of plasminogen activator inhibitor-1 (PAI-1) which inhibits various tumor cell lines with IC50 values in the range of 9.7 and 60.3 uM. TM-5441 has the potential to be used to treat cancer and prevent diabetic kidney injury, because numerous studies have shown a paradoxical positive correlation between elevated levels of PAI-1 in tumors and blood of cancer patients with poor clinical outcome, also PAI-1 is increasingly recognized as a key factor in extracellular matrix (ECM) accumulation in diabetic nephropathy. TM5441 protects against high-fat diet-induced obesity and adipocyte injury in mice. 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.

References: PLoS One. 2016 Jun 3; 11(6):e0157012; PLoS One. 2015 Jul 24; 10(7):e0133786.