PB28 (dihydrochloride)

PB28 dihydrochloride, a cyclohexylpiperazine derivative, is a high affinity and selective sigma 2 (σ2) receptor agonist with a K_i of 0.68 nM. PB28 dihydrochloride is also a σ1 antagonist with a K_i of 0.38 nM. PB28 dihydrochloride is less affinity for other receptors. PB28 dihydrochloride inhibits electrically evoked twitch in guinea pig bladder and ileum with EC₅₀ values of 2.62 μM and 3.96 μM, respectively. PB28 dihydrochloride can modulate SARS-CoV-2-human protein-protein interaction. PB28 dihydrochloride induces caspase-independent apoptosis and has antitumor activity^{[1][2][3][4][5]}. In Vitro: PB28 (15-25 nM; 24-48 hours; MCF7 and MCF7 ADR cells) dihydrochloride treatment shows an accumulation in the G0-G1 phase for MCF7 and MCF7 ADR cells that are time and concentration independent^[1].
PB28 dihydrochloride 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 dihydrochloride inhibits cell growth of MCF7 and MCF7 ADR cells with IC₅₀s of 25 nM and 15 nM, respectively after 2-day treatment^[1].
PB28 dihydrochloride induces apoptosis through a caspase-independent pathway^[1].
PB28 dihydrochloride also reduces P-gp expression in a concentration- and time-dependent manner (approximately 60% in MCF7 and 90% in MCF7 ADR)^[1].
PB28 dihydrochloride displays antiproliferative and cytotoxic effects in both C6 rat glioma and SK-N-SH human neuroblastoma cell lines^[1]. In Vivo: PB28 (10.7 mg/mL; intraperitoneal injection; daily; for two weeks; C57BL/6 female mice) dihydrochloride treatment inhibits tumor growth in Panc02 tumor burden mice. PB28 also conferres a survival advantage for mice^[2].