PB28 is a cyclohexylpiperazine derivative that functions as a potent and highly selective agonist of the sigma 2 (σ2) receptor, exhibiting a Ki (binding affinity) of 0.68 nM. At the same time, PB28 acts as an antagonist of the sigma 1 (σ1) receptor, with a Ki of 0.38 nM. PB28 demonstrates a lower affinity for other receptors. It effectively inhibits electrically evoked twitch in both the guinea pig bladder (EC50 value of 2.62 μM) and ileum (EC50 value of 3.96 μM). Moreover, PB28 exhibits the ability to modulate protein-protein interaction between SARS-CoV-2 and human cells. Additionally, PB28 triggers caspase-independent apoptosis and possesses significant antitumor activity.

σ2 receptor:0.68 nM (Ki), σ1 receptor:0.38 nM (Ki)

PB28 (15-25 nM; 24-48 hours; MCF7 and MCF7 ADR cells) treatment shows an accumulation in the G0-G1 phase for MCF7 and MCF7 ADR cells that are time and concentration independent[1]. PB28 has a higher σ2 receptor affinity expressed as K i (0.28 nM and 0.17 nM in MCF7 and MCF7 ADR cells, respectively) than σ1 receptor affinity (13.0 nMand 10.0 nM, respectively)[1]. PB28 inhibits cell growth of MCF7 and MCF7 ADR cells with IC 50 s of 25 nM and 15 nM, respectively after 2-day treatment[1]. PB28 induces apoptosis through a caspase-independent pathway[1]. PB28 also reduces P-gp expression in a concentration- and time-dependent manner (approximately 60% in MCF7 and 90% in MCF7 ADR)[1]. PB28 displays antiproliferative and cytotoxic effects in both C6 rat glioma and SK-N-SH human neuroblastoma cell lines[1]. Cell Cycle Analysis[1]Cell Line: MCF7 and MCF7 ADR cells Concentration: 25 nM and 15 nM Incubation Time: 24 hours, 48 hours Result: Showed an accumulation in the G0-G1 phase for MCF7 and MCF7 ADR cells that were time and concentration independent.

PB28 (10.7 mg/mL; intraperitoneal injection; daily; for two weeks; C57BL/6 female mice) treatment inhibits tumor growth in Panc02 tumor burden mice. PB28 also conferres a survival advantage for mice[2]. Animal Model: C57BL/6 female mice (10 weeks old) injected with Panc02 cells[2]Dosage: 10.7 mg/mL Administration: Intraperitoneal injection; daily; for two weeks Result: Inhibited tumor growth in Panc02 tumor burden mice.