TM5441

TM5441 is an orally bioavailable inhibitor of plasminogen activator inhibitor 1 (PAI-1), a serine-protease inhibitor involved in thrombosis.^1,2 It decreases survival of HT1080, HCT116, Daoy, MDA-MB-231, and Jurkat cancer cells with IC₅₀ values ranging from 13.9 to 51.1 µM.¹ TM5441 inhibits branching of human umbilical vein endothelial cells (HUVECs) in a vasculature assay in vitro when used at a concentration of 50 µM but does not affect HUVEC survival or apoptosis. It also disrupts tumor vasculature in HT1080 and HCT116 mouse xenograft models when used at a dose of 20 mg/kg per day. TM5441 prevents hypertension and cardiac hypertrophy and reduces periaortic fibrosis induced by L-NAME (Item No. 80210).² It protects against high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) in mice when administered concurrently with a high-fat diet or after glucose tolerance has developed.³ TM5441 also increases median lifespan by 4-fold and reduces signs of senescence in Klotho-deficient mice, a mouse model of aging.⁴

WARNING This product is not for human or veterinary use.

1. Placencio, V.R., Ichimura, A., Miyata, T., et al. Small molecule inhibitors of plasminogen activator inhibitor-1 elicit anti-tumorigenic and anti-angiogenic activity. PLoS One 10(7), e0133786 (2015).

2. Boe, A.E., Eren, M., Murphy, S.B., et al. Plasminogen activator inhibitor-1 antagonist TM5441 attenuates N^ω-nitro-L-arginine methyl ester-induced hypertension and vascular senescence. Circulation 128(21), 2318-2324 (2013).

3. Lee, S.M., Dorotea, D., Jung, I., et al. TM5441, a plasminogen activator inhibitor-1 inhibitor, protects against high fat diet-induced non-alcoholic fatty liver disease. Oncotarget 8(52), 89746-89760 (2017).

4. Eren, M., Boe, A.E., Murphy, S.B., et al. PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice. Proc. Natl. Acad. Sci. USA 111(19), 7090-7095 (2014).