JR1-157 is a potent selective sigma 2 receptor (σ2R) ligand with Ki value of 47 nM, >10-fold selectivity over σ1R.
JR1-157 inhibits multiple pancreatic cell growth with IC50 of 1.2 uM (MIA PaCa-2) in MTT assays, inhibits colony formation of MIA PaCa-2 cells with KRAS G12C mutation more potently, as compared to other tested pancreatic cancer cell lines.
JR1-157 displays >10 -fold selectivity over a panel of 45 GPCRs and related transmembrane targets.
JR1-157 is significantly less toxic than gemcitabine in HEK-293 and HPDE cells.
JR1-157 is slightly antagonistic to σ2R agonist siramesine and additive to σ2R antagonist roluperidone in MIA PaCa-2 cells, increases protein levels of GRP78 and autophagy marker (LC3B).
JR1-157 (10 uM) induces apoptosis in MIA PaCa-2 and HCT-116 cells, arrests cells in the G0/G1 phase.
JR1-157 (30 mg/kg) with copper sulfate (3 mg/kg) via p.o. administration delays pancreatic tumor growth in vivo.
