Demethylasterriquinone B1 is a cell-permeable asymmetrical bis-indolylquinone insulin mimic with anti-diabetic activity in animal models. Selectively stimulates insulin receptor (IR) tyrosine kinase activity (EC50 ~ 6 μM in CHOIR cells), while showing little effect towards IGF-1R, EGFR, or PDGFR. Demethylasterriquinone B1 also acts as an agonist for Trk A, Trk B and Trk C (the neurotrophin receptors TrkA, B, and C) in both cortical neurons and dorsal root ganglion neurons (~ 20 μM). DMAQ-B1 and insulin show differential effects on cellular gene expression profiles and DMAQ-B1 is a more selective agonist than insulin for the IR-mediated activation of PI-3 kinase/Akt pathway. Demethylasterriquinone B1 is an activator of insulin R.
