SKF-96365 hydrochloride 是store-operated Ca2+entry抑制剂，也是TRP channel阻滞剂。它显著抑制豚鼠离体心脏 HERG、hKCNQ1/hKCNE1、hKir2.1 和 hKv4.3 电流，延长QTc间期。它通过诱导结直肠癌细胞的细胞周期阻滞和凋亡起抗肿瘤作用。

SKF-96365, a SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal Y cells. SKF-96365 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 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 inhibited hERG current in a concentration-dependent manner.

SKF-96365 exhibits protective activity against MPP+ injury in PC12 cells and significantly inhibits apoptotic cell death in PC12 cells after MPP+ administration. SKF-96365 does not exert effects on necrotic cell death induced by MPP+ insult in PC12 cells. Because of its non-selective activity, SKF-96365 has been demonstrated to have effects on multiple other Ca2+ channels: it not only blocks high-voltage-activated (HVA) Ca2+ channels at typically utilized test concentrations, but also potently inhibits low-voltage -activated (LVA) T-type Ca2+ channels in HEK293 cells. The exact effect of SKF-96365 on intracellular calcium homeostasis might dependent on cell types and experimental models used[2].

SKF-96365 treatment inhibited the calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ)/AKT signaling cascade in vitro and in vivo[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)

130495-35-1

C22H27ClN2O3

402.92

SKF96365;1-[2-(4-甲氧基)-2-[3-(4-甲氧基苯基)丙氧基]乙基]咪唑

DMSO:198.6 mM
H2O:198.6 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years