Background:

GSK 650394 is a small molecule inhibitor of serum and glucocorticoid-regulated kinase 1 (SGK1) with IC50 value of 13nM [1].

Sgk1 gene is a target gene of androgen. Knockdown of SGK1 expression attenuates androgen-mediated growth of the prostate cancer cell line. Thus, the inhibition of SGK1 is a novel mechanism for the treatment of prostate cancer. GSK 650394 is a competitive inhibitor of SGK1. It shows potent inhibitory activity against the purified SGK1 with IC50 value of 13nM in a fluorescence polarization assay. In the activity-based scintillation proximity assay, GSK 650394 prevents the phosphorylation activity of SGK1 and SGK2 with IC50 values of 62nM and 103nM, respectively. Moreover, GSK 650394 suppresses the androgen-mediated increase of Nedd4-2 phosphorylation in LNCaP cells. It also significantly inhibits cell growth stimulated by androgen with IC50 value of about 1μM [1].

参考文献:
[1] Sherk A B, Frigo D E, Schnackenberg C G, et al. Development of a small-molecule serum-and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic. Cancer research, 2008, 68(18): 7475-7483.