PB 28 dihydrochloride, a cyclohexylpiperazine derivative, is sigma (σ) receptor ligand, acting as a σ₂ receptor agonist with a Ki value of 0.68 nM, as well as a σ₁ receptor antagonist with a Ki of 0.38 nM. The σ receptor, composed of σ₁ and σ₂ subtypes, is present with high density in central nervous system and peripheral organs, and overexpressed in many tumor cell lines. Selective σ₂ receptor agonists have been proposed as anticancer drugs, while selective σ₁ receptor ligands have been proposed to develop new classes of central nervous system agents for neuroprotection, anxiety, depression, psychosis, as well as learning and memory improvement.

References:

1. Berardi F, Abate C, Ferorelli S, et al. Exploring the importance of piperazine N-atoms for sigma(2) receptor affinity and activity in a series of analogs of 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28). Journal of Medicinal Chemistry, 2009, 52(23): 7817-7828.

2. Azzariti A, Colabufo NA, Berardi F, et al. Cyclohexylpiperazine derivative PB28, a sigma2 agonist and sigma1 antagonist receptor, inhibits cell growth, modulates P-glycoprotein, and synergizes with anthracyclines in breast cancer. Molecular Cancer Therapeutics, 2006, 5(7): 1807-1816.

3. Pati ML, Hornick JR, Niso M, et al. Sigma-2 receptor agonist derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) induce cell death via mitochondrial superoxide production and caspase activation in pancreatic cancer. BMC Cancer, 2017, 17(1): 51.