TMPA

TMPA is a high-affinity Nur77 antagonist that binds to Nur77 leading to the release and shuttling of LKB1 in the cytoplasm to activate AMPKα. TMPA effectively lowers blood glucose and attenuates insulin resistance in type II db/db, high-fat diet and streptozotocin-induced diabetic mice. TMPA reduces RICD (restimulation-induced cell death) in human T cells, can also be used in studies of cancer and T-cell apoptosis dysregulation.

In Vitro

TMPA (5, 10, 20, 40, 80 μM; 6 h or 10 μM; 0.5, 1, 3, 6, 12, 24, 36, 48 h) antagonizes the Nur77-LKB1 interaction in a dose- and time-dependent manner in hepatic LO2 cells. ?\nTMPA (10 μM; 6 h) enhances the LKB1-AMPKα interaction but decreases the LKB1-Nur77 interaction under physio logical conditions in Lo2 cells. ?\nTMPA binds directly to LBD in specific conformation. ?\nTMPA (10, 20 μM; 6 h) induces LKB1 nuclear export to activate AMPKα in Lo2 cells. ?\nTMPA (10, 50, 100 μM; 4 h) impairs human T-cell RICD (restimulation-induced cell death). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: T cells Concentration: 10, 50, 100 µM Incubation Time: 4 h Result: Significantly reduced T-cell RICD in a dose-dependent manner. Western Blot AnalysisCell Line: Hepatic LO2 cells Concentration: 10, 20 µM Incubation Time: 6 h Result: Led to an increase of LKB1 phosphorylation at Ser428. Western Blot AnalysisCell Line: Hepatic LO2 cells Concentration: 5, 10, 20, 40, 80 µM Incubation Time: 6 h Result: Increased the amount of phosphorylation of AmPKα in a dose- and time-dependent manner. Rescued the LKB1-AmPKα interaction by reducing the nur77-lKb1 interaction when at 10 µM.

In Vivo

TMPA (50 mg/kg; i.p.; single daily for 19 days) is capable of lowering blood glucose and improving glucose tolerance in type II diabetic mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male C57BL/KsJ-Lepr db /Lepr db (db/db) mice (10-week-old; type II diabetic model) . Dosage: 50 mg/kg Administration: Intraperitoneal injection; single daily for 19 days. Result: Significantly reduced blood glucose at day 7 and persisted during the remainder of the test. Increased the amount of phosphorylated AMPKα in the liver of mice.