GSK-3 Inhibitor XV

Description

The racemic mixture of a cell-permeable pyridocarbazolo-cyclopentadienyl Ruthenium complex that acts as a reversible, ATP-competitive, and highly potent inhibitor of GSK-3 (IC50=0.4 and 0.6 nM for GSK-3α and GSK-3β, respectively) with ∼5-fold selectivity over PIM-1 kinase (IC50=3 nM). Studies using isolated enantiomers have shown that the (R)-enantiomer is GSK-3-selective (IC50=0.35, 0.55, and 35 nM for GSK-3α GSK-3β, and Pim-1, respectively) and interferes with normal zebrafish embryo development (1 µM), while the (S)-enantiomer is Pim-1-selective (IC50=80, 90, and 3 nM for GSK-3α GSK-3β, and Pim-1, respectively) and exhibits no effect in embryo development at the same dosage.