PB28 dihydrochloride

Description

PB28 (172907-03-8) is a very potent high affinity (Ki = 5.3 nM1, 0.34 nM2) σ2 agonist. Selective for σ2 over σ1 (approx 30-40x).1,2 PB28 inhibited cell growth in MCF7 and MCF7 ADR breast cancer cells and displayed strong synergism with doxorubicin.3 PB28 potently inhibited Kv2.1 currents in a σ-independent manner.4 PB28 was recently found to have potent (IC50 = 280 nM) anti-SARS-CoV2 activity.5

Uses

PB28 dihydrochloride, a cyclohexylpiperazine derivative, is a high affinity and selective sigma 2 (σ2) receptor agonist with a Ki of 0.68 nM. PB28 dihydrochloride is also a σ1 antagonist with a Ki 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 vivo

storage

Desiccate at +4°C

References

[1] FRANCESCO BERARDI. New σ and 5-HT1A Receptor Ligands: ω-(Tetralin-1-yl)-n-alkylamine Derivatives[J]. Journal of Medicinal Chemistry, 1996, 39 1: 176-182. DOI:10.1021/jm950409c
[2] FRANCESCO BERARDI. 4-(Tetralin-1-yl)- and 4-(Naphthalen-1-yl)alkyl Derivatives of 1-Cyclohexylpiperazine as σ Receptor Ligands with Agonist σ2 Activity[J]. Journal of Medicinal Chemistry, 2004, 47 9: 2308-2317. DOI:10.1021/jm031026e
[3] AMALIA AZZARITI. Cyclohexylpiperazine derivative PB28, a sigma2 agonist and sigma1 antagonist receptor, inhibits cell growth, modulates P-glycoprotein, and synergizes with anthracyclines in breast cancer.[J]. Molecular Cancer Therapeutics, 2006, 5 7: 1807-1816. DOI:10.1158/1535-7163.mct-05-0402
[4] XINYING LIU. Potential independent action of sigma receptor ligands through inhibition of the Kv2.1 channel.[J]. Oncotarget, 2017, 8 35: 59345-59358. DOI:10.18632/oncotarget.19581
[5] DAVID E. GORDON. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing[J]. Nature, 2020, 583 7816: 459-468. DOI:10.1038/s41586-020-2286-9