Indirubin-3'-monoxime

Indirubin-3'-monoxime is a potent GSK-3β inhibitor, and weakly inhibits 5-Lipoxygenase, with IC₅₀s of 22 nM and 7.8-10 µM, respectively; Indirubin-3'-monoxime also shows inhibitory activities against CDK5/p25 and CDK1/cyclin B, with IC₅₀s of 100 and 180 nM. IC50 & Target: IC50: 22 nM (GSK-3β), 100 nM (CDK5/p25), 180 nM (CDK1/cyclin B)^[1], 7.8-10 µM (5-Lipoxygenase)^[3] In Vitro: Indirubin-3'-monoxime inhibits GSK-3β by competing with ATP, with K_i of 0.85 μM, and K_m of 110 μM. Indirubin-3'-monoxime also inhibits tau phosphorylation by GSK-3β, with an IC₅₀ value of around 100 nM. Indirubin-3'-monoxime completely inhibits the phosphorylation of the AT100 epitope^[1]. Indirubin-3'-monoxime inhibits vascular smooth muscle cell (VSMC) proliferation with IC₅₀ of ∼2 µM. Indirubin-3'-monoxime blunts migration of VSMC stimulated with the PDGF. Indirubin-3'-monoxime interferes with the migratory response in VSMC, and also suppresses the production of pro-migratory LT in monocytes. Moreover, Indirubin-3'-monoxime inhibits 5-lipoxygenase (5-LO) product synthesis in monocytes and neutrophils, with the same potency (IC₅₀=5.0±1.1 and 3.7±1.2 µM, respectively). Indirubin-3'-monoxime is an inhibitor of 5-LO, with IC₅₀ of 7.8-10 µM in cell-free assay^[3]. In Vivo: Indirubin-3'-monoxime (0.1, 0.2 and 0.4 mg/kg, i.p) dose dependently reverses the cognitive impairment and combats the elevated oxidative stress markers in HFD fed mice. Indirubin-3'-monoxime also dose dependently lowers the serum glucose, TGs, TC and insulin levels, and improves the β-cell functioning in HFD fed mice. Moreover, Indirubin-3'-monoxime treatment significantly decreases HOMA-IR levels compared to HFD group. Indirubin-3'-monoxime (0.4 mg/kg) significantly attenuates the increased EL in the HFD group^[2].