SKF-96365 hydrochloride (SKF96365) , a SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal Y cells. SKF-96365 hydrochloride can induce cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 hydrochloride treatment inhibited the calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ)/AKT signaling cascade in vitro and in vivo. Overexpression of CaMKIIγ or AKT abolished the effects of SKF-96365 on Y cells, suggesting a critical role of the CaMKIIγ/AKT signaling pathway in SFK-96365-induced biological effects. SKF-96365 hydrochloride inhibited hERG current in a concentration-dependent manner.

SKF-96365 在PC12细胞中对MPP+引起的损伤显示出保护作用，显著抑制了MPP+处理后PC12细胞的凋亡死亡，并且在PC12细胞中不影响MPP+诱导的坏死性死亡。由于其非选择性活性，SKF-96365已被证明对多种Ca2+通道有影响：它不仅能在常用测试浓度下阻断高电压激活（HVA）Ca2+通道，也能强效抑制在HEK293细胞中的低电压激活（LVA）T型Ca2+通道。SKF-96365对细胞内钙稳态的具体作用可能依赖于细胞类型和所使用的实验模型[2]。

SKF-96365处理在体外和体内抑制了钙/钙调蛋白依赖性蛋白激酶IIγ（CaMKIIγ）/AKT信号通路[4]。

To investigate whether SKF-96365 could protect PC12 cells from injury induced by MPP+ insult, cultured PC12 cells are pretreated with SKF-96365 in different concentrations (1 µM, 10 µM or 50 µM) 30 min before MPP+ addition. The cells viability is measured 24 h after MPP+ insult by using the cell proliferation reagent WST-1. (Only for Reference)