Biochemicals & reagents
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
Siramesine is a σ2 selective agonist with IC50’s for σ1 = 17nM and σ2 = 0.2nM (1). This compound produced non-sedating potent and long-last anxiolytic effects in rodents (2), it induced caspase-independent programmed cell death in various cancer cell lines via increased levels of ROS and lysosomal leakage (3,4,5) and 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).