Stattic

Stattic, the first nonpeptidic small molecule, potently inhibits STAT3 activation and nuclear translocation with IC50 of 5.1 μM, highly selectivity over STAT1.(In Vitro):Stattic (20 μM; 24 hours) inhibits STAT3 phosphorylation (Y705) and selectively inhibits P-STAT3 as demonstrated by the lack of inhibition of P-ERK1/2 in ALDH+ and D44+/CD24+ subpopulations of Panc-1 and HPAC pancreatic cancer cell lines.Stattic (2.5, 5, 10 μM; for 4 h) significantly reduces the nuclear level of pSTAT3 and survivin in PC3M-1E8 cells at 10 μM. Stattic (2.5-10 μM; for 24 h) inhibits IL-6-induced STAT3 activation in a dose-dependent manner.Stattic (2.5, 5, 10 μM; for 48 h) suppresses both the growth and induces apoptosis prostate cancer cells (PC3M-1E8 cells) with 10 μM. Stattic does not induce significant cell apoptosis with 2.5 μM, 5 μM.Stattic (2.5, 5, 10 μM; for 48 h) shows significant S phase accumulation.Stattic can not lead to significant morphological changes or apoptosis and has little STAT3 phosphorylation in A2780 cells and HUVECs.(In Vivo):Stattic (10 mg/kg; i.p.; three times per week for 10 week) ameliorates the renal dysfunction in Alport syndrome (AS) mice.