GSK2334470 is a highly specific and potent inhibitor of PDK1 with an IC50 of 10 nM.
IC50&Target
IC50: 10 nM(PDK1)
体外研究
Small molecule GSK2334470 inhibits PDK1 with an IC50 of ~10 nM, but does not suppress the activity of 93 other protein kinases including 13 AGC-kinases most related to PDK1 at 500-fold higher concentrations. Addition of GSK2334470 ablates T-loop residue phosphorylation and activation of SGK isoforms and S6K1 induced by serum or IGF-1 (insulin-like growth factor 1). GSK2334470 and AZD8055 effectively inhibite phosphorylation of PDK1 and mTOR, respectively, and induce higher G0–G1 ratio in LAN-1-MK than that in LAN-1 as well. PDK1 and mTOR inhibitors effecte on phosphorylation of GSK3β in some of resistant sublines.
体内研究
The efficacy of the PDK1 inhibitor (PDKi) GSK2334470 is tested in newborn Braf::Ptenmice subjected to systemic administration of 4-HT. Twice weekly administration of PDK1 results in marked inhibition of pigmented lesions and concomitant melanomagenesis, as well as significant inhibition of lung metastases, seen by H&E staining-based quantification (~80%), and lymph node metastases as by S100 immunostaining, similar to the phenotype seen upon genetic ablation of Pdk1.
分子式
C25H34N8O
分子量
462.59
CAS号
1227911-45-6
运输条件
Room temperature in continental US; may vary elsewhere.