S1RA

Uses

S1RA (E-52862) is a highly selective σ1 receptor (σ1R) antagonist with Kis of 17 nM and 23.5 nM for human σ1R and guinea pig σ1R, respectively. S1RA has Moderate antagonistic activity for human 5-HT2B receptor (Ki= 328 nM). S1RA has antinociceptive effects in neuropathic pain models. S1RA prevents mechanical and cold hypersensitivity in Oxaliplatin (HY-17371)-treated mice[1][2].

Biological Activity

s1ra is a potent and selective antagonist of σ1 receptor (σ1r) with ki value of 17nm [1].s1ra is the first σ1 receptor antagonist with potent antinociceptive activities in various pain models. in the binding assay, s1ra shows good affinity to human σ1 receptor transfected in hek293 membranes with ki value of 17nm. the ki value for guinea pig brain membrane σ1 receptor is higher than 1μm. s1ra also shows no significant affinity to another 170 molecular targets including receptors, ion channels and enzymes [1, 2].in the mouse tests, s1ra exhibits potent analgesic effects on capsaicin-induced mechanical hypersensitivity and formalin-induced pain. besides that, s1ra inhibits both mechanical allodynia and thermal hypersensitivity with ed50 values of 23.4mg/kg and 18.8mg/kg in the partial sciatic nerve ligation model in mice [1].

in vivo

IC 50

human σ1R: 17 nM (Ki); guinea pig σ1R: 23.5 nM (Ki); guinea pig σ2R: >1000 nM (Ki); rat σ2R: 9300 nM (Ki); human 5-HT_2B Receptor: 328 nM (Ki)

References

[1] díaz j l, cuberes r, berrocal j, et al. synthesis and biological evaluation of the 1-arylpyrazole class of σ1 receptor antagonists: identification of 4-{2-[5-methyl-1-(naphthalen-2-yl)-1 h-pyrazol-3-yloxy] ethyl} morpholine (s1ra, e-52862). journal of medicinal chemistry, 2012, 55(19): 8211-8224.
[2] wunsch b. the σ1 receptor antagonist s1ra is a promising candidate for the treatment of neurogenic painj. journal of medicinal chemistry, 2012, 55(19): 8209-8210.