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TMPA is a novel small molecule that binds to orphan Nuclear Receptor Nur77 with high affinity (Kd = 1.45 ± 0.35 μM), and interferes with the Nur77-LKB1 interaction. TMPA’s binding to Nur77 results in the release and shuttling of LKB1 to the cytoplasm to phosphorylate AMPKα. TMPA treatment can effectively reduce blood glucose and alleviate insulin resistance in type II db/db and high-fat diet– and streptozotocin-induced diabetic mice but not in diabetic littermates with the Nur77 gene knocked out. TMPA may serve as a powerful chemical tool to attain a mechanistic understanding of the regulation of LKB1-AMPK axis and a lead compound for the design and development of therapeutics to treat metabolic diseases.

How to Use:

• In vitro: TMPA was used at 10 μM final concentration in vitro and in cellular assays.
• In vivo: TMPA was intraperitoneally (IP) dosed to mice at 50 mg/kg once per day. Formulation: 5.0% (v/v) Tween-80 in 0.9% (w/v) saline.

Reference:

1. 1. Zhang YY, et al. The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK. (2012) Nat Chem Biol. 8(11):897-904.

Products are for research use only. Not for human use.