SI113, a specific inhibitor of the Sgk1 kinase activity that counteracts cancer cell proliferation.

摘要: Background/Aims: Published observations on serum and glucocorticoid regulated kinase 1 (Sgk1) knockout murine models Sgk1-specific RNA silencing in the RKO human colon carcinoma cell line point to this as a central player carcinogenesis resistance taxanes. Methods: By vitro activity inhibition assays, cycle viability analysis cancer model systems, we describe biologic effects of recently identified inhibitor, SI113, characterized by substituted pyrazolo[3,4-d]pyrimidine scaffold, that shows specificity for Sgk1. Results: SI113 was able inhibit growth cells derived from tumors with different origins. In cells, inhibitor blocked insulin-dependent phosphorylation Sgk1 substrate Mdm2, main regulator p53 protein stability, induced necrosis apoptosis when used single agent. Finally, potentiated paclitaxel viability. Conclusion: Since appears be effective inducing death potentiating sensitivity, believe new molecule could efficiently employed, alone or combination paclitaxel, chemotherapy.