Merck, 492910-10MG, Nur77 LBD Antagonist, TMPA - Calbiochem

General description
A cell-permeable phenylacetate compound that blocks Nur77 (TR3) LKB1 nuclear-sequestering function by antagonizing Nur77-LKB1 interaction via direct binding at the LKB1 LBD/ligand binding domain (Kd = 0.14 and 0.25 µM, respectively, against 5 µM LKB1 binding to 5 µM full-length Nur77 or Nur77 LBD). Shown to induce LKB1 Ser428 phosphorylation (10 & 20 µM for 6 hr) and LKB1 nuclear-to-cytosol translocation in hepatic LO2 cells, resulting in enhanced phosphorylations of LKB1 cytosolic effectors AMPKα (Thr172) and MARK (Thr215, Thr208, and Thr234 of MARK1, MARK2, and MARK3, respectively), without affecting Nur77 transactivation activity. Likewise, daily i.p. dosing (50 mg/kg for 19 d) results in greatly enhanced liver LKB1 Ser428/AMPKα Thr172 phosphorylations only in Nr4a1+/+, but not Nur77-null Nr4a1-/-, diabetic db/db mice in vivo, effectively lowering fasting blood glucose and insulin level, and enhancing glucose tolerance in db/db mice. Also reported to lower fasting blood glucose level in high fat diet-fed Nr4a1+/+ mice treated with STZ (Cat. No. 572201) to induce type II diabetes.