UCF 101 is a specific inhibitor of HtrA2 and reduces apoptosis in PC12 cells.

His-Omi:9.5 μM (IC50)

PC12 cells treated with 60 μM 6-OHDA for 24 h had significantly decreased cell viability compared to that of controls. A low concentration (2.5 μM) of UCF 101 decreased the apoptosis rate of the PD cell model, but a high concentration (≥10 μM) increased the apoptosis rate, compared to that of controls. 6-OHDA upregulated the expression of HtrA2, α-syn, CHOP, Grp78 and active caspase-3 and reduced the levels of TH and XIAP[3].

Administration of UCF 101 shortly before reperfusion reduced postischemic myocardial apoptosis in a dose-dependent fashion, with the maximal protective effect observed at a dose of 1.5 μmol/kg. This dose of UCF 101 (ie, 1.5 μmol/kg) was used in all subsequent experiments. To further establish that inhibition of Omi/HtrA2 protease activity led to significant inhibition of apoptosis, the effect of UCF 101 on DNA ladder formation, a hallmark of apoptotic cell death, was determined. 30 minutes of ischemia followed by 3 hours of reperfusion resulted in significant DNA fragmentation, which was significantly reduced by treatment with UCF 101 before reperfusion[2].UCF 101 reduced the level of ERS and apoptosis in vivo. The ratio of p-GSK3β (Tyr216 to Ser9) increased in PD rats[3].