SIRAMESINE

Description

Siramesine (Lu 28-179, 147817-50-3) is a σ2 selective agonist?(IC50’s: σ1 = 17nM, σ2 = 0.2nM).1?It produced non-sedating potent and long-last anxiolytic effects in rodents.2?Siramesine induced caspase-independent programmed cell death in various cancer cell lines?via?increased levels of ROS and lysosomal leakage.3,4,5?Mitochondrial destabilization via loss of membrane potential and increased ROS has also been offered as a mechanism of action for the triggering of cell death by Siramesine.6

The Uses of SIRAMESINE

Treatment of prostate cancer.

brand name

Provenge (Dendreon).

References

1) Perregaard?et al.?(1995),?Sigma ligands with subnanomolar affinity and preference for the sigma 2 binding site. 1. 3-(omega-aminoalkyl)-1H-indoles; J. Med. Chem.?38?1998 2) Sanchez?et al.?(1997),?The selective sigma2-ligand Lu 280179 has potent anxiolytic effects in rodents; J. Pharmacol. Exp. Ther.?283?1323 3) Ostenfeld?et al.?(2005),?Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress;?Cancer Res.?65?8975 4) Ostenfeld et al. (2008),?Anti-cancer agent siramesine is a lysosomotropic detergent that induces cytoprotective autophagosome accumulation; Autophagy?4?487 5) Dielschneider?et al.?(2016),?Lysosomotropic agents selectively target chronic lymphocytic leukemia cells due to altered sphingolipid metabolism; Leukemia?30?1290 6) Cesen?et al.?(2013),?Siramesine triggers cell death through destabilization of mitochondria, but not lysosomes; Cell Death Dis.?4?e818