GSK-3β Inhibitor XXIV

The racemic mixture of a cell-permeable oxadiazolo-benzofuranylphenylsulfoxide that inhibits GSK-3β (IC₅₀ = 35, 34, and 140 nM using the racemate, the (S), and the (R) enantiomer, respectively) in a highly selective manner as evidenced by its eutomer′s inability to inhibit 10 other serine/threonine and 12 other tyrosine kinases even at concentrations as high as 10 µM. Reported to exhibit good aqueous solubility (38 µg racemate/ml pH 6.8 buffer) and pharmacokinetic properties, being orally active in both rats and mice in vivo (Plasma AUC_0-24h = 1380.6 and 457 ng•h/mL, respectively; 3 mg eutomer/kg via p.o.). The eutomer is also shown to be blood-brain-permeant in mice (brain AUC_0-24h = 734 ng•h/mL; 3 mg/kg via p.o.) and oral dosing 30 min prior to CWS (cold water stress; 4 min below-neck inversion in 1-2 °C water) is demonstrated to reduce brain tau Thr205 phosphorylation (by 35%; 10 min post CWS) in mice in vivo.

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Saitoh, M., et al. 2009. J. Med. Chem.52, 6270.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)