PB28 dihydrochloride is a selective and potent sigma 2 (σ2) receptor agonist and σ1 receptor antagonist with anti-SARS-CoV-2 activity and anti-tumor activity, which inhibits cell proliferation and invasion and suppresses SKF by modulating the PI3K-AKT-mTOR signaling pathway in renal cancer. It inhibits cell proliferation and invasion by regulating the PI3K-AKT-mTOR signaling pathway in renal cancer, inhibits calcium release from the endoplasmic reticulum of SK-N-SH neuroblastoma cells, and induces non-caspase-dependent apoptosis.

MCF-7/ADR cells:15 nM, MCF-7/ADR cells:0.17 nM (Ki), MCF-7 cells:0.28 nM (Ki), MCF-7 cells:25 nM

PB28 dihydrochloride has a higher affinity for the σ2 receptor, with Ki values of 0.28 nM and 0.17 nM in MCF7 and MCF7 ADR cells, respectively.Accumulation of the two types of cells in the G0-G1 phase was observed after treatment of MCF7 and MCF7 ADR cells for 24-48 h at concentrations of 15-25 nM, an effect that was not affected by time and concentration changes. and concentration changes. After 2 days of incubation, PB28 dihydrochloride effectively inhibited the growth of MCF7 and MCF7 ADR cells with IC50s of 25 nM and 15 nM, respectively.This compound triggers apoptosis through a non-cysteoaspartase-dependent pathway.
In addition, PB28 dihydrochloride significantly reduced P-gp expression in a concentration- and time-dependent manner by approximately 60% in MCF7 cells and 90% in MCF7 ADR cells. PB28 dihydrochloride also exhibited significant antiproliferative toxicity in the C6 rat glioma cell line and the SK-N-SH human neuroblastoma cell line. [1]

PB28 dihydrochloride was injected daily intraperitoneally at a concentration of 10.7 mg/mL for two weeks into C57BL/6 female mice and was shown to be effective in inhibiting tumor growth in Panc02 tumor-loaded mice. In addition, PB28 dihydrochloride significantly increased the survival rate of mice. [2]