tcsc1853 GSK 650394

GSK 650394 is a novel SGK inhibitor with IC₅₀ of 62 nM and 103 nM for SGK1 and SGK2 in the SPA assay respectively.

IC50 & Target: IC50: 62 nM (SGK1), 103 nM (SGK2)

In Vitro: GSK650394 is relatively non-toxic, with LC₅₀ values of 41 μM in M1 cells (68 times its activity IC₅₀) and a LC₅₀ greater than 100 μM in HeLa cells. GSK650394 inhibits SGK1-mediated epithelial transport with an IC₅₀ of 0.6 μM in the SCC assay. GSK650394 inhibits the growth of LNCaP cells with IC₅₀ of approximately 1 μM^[1]. GSK650394A inhibits the insulin-induced phosphorylation of PKB-Ser⁴⁷³ at 3 µM, and essentially abolishes this response at 10 µM. GSK650394A (1-10 µM) does not alter the phosphorylation of PRAS40-Ser246 in hormone-deprived cells or prevent the insulin-induced phosphorylation of this residue^[2].

In Vivo: GSK650394 (1, 10, and 30 μM, 10 μL/rat, intrathecally) dose-dependently prevents CFA-induced pain behavior and the associates SGK1 phosphorylation, GluR1 trafficking, and protein-protein interactions at 1 day after CFA administration^[3]. GSK650394 at concentrations of 10, 30, and 100 nM (10 μL), but not vehicle solution (SNL 3D+Veh and SNL 7D+Veh, respectively), dose-dependently increases the withdrawal latency of the ipsilateral hindpaw at 1-3 and 1-5 h after injection at days 3 and 7 postsurgery (SNL 3D+GSK and SNL 7D+GSK, respectively). GSK650394 (from day 0 to 6 postsurgery; 100 nM, 10 μL, i.t.) administration alleviates SNL-induced allodynia at days 3, 5, and 7 postsurgery in SNL animals^[4].