Synonym
PB28 dihydrochloride; PB28 HCl;
IUPAC/Chemical Name
1-Cyclohexyl-4-(3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl)piperazine dihydrochloride
InChi Key
DSRBJOQIBXACIV-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H38N2O.2ClH/c1-27-24-14-6-12-22-20(8-5-13-23(22)24)9-7-15-25-16-18-26(19-17-25)21-10-3-2-4-11-21;;/h6,12,14,20-21H,2-5,7-11,13,15-19H2,1H3;2*1H
SMILES Code
COC1=CC=CC2=C1CCCC2CCCN3CCN(C4CCCCC4)CC3.[H]Cl.[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
PB28 dihydrochloride, a cyclohexylpiperazine derivative, is a high affinity and selective sigma 2 (σ2) receptor agonist with a Ki of 0.68 nM.
In vitro activity:
This study verified whether a mixed sigma(2) agonist/sigma(1) antagonist, PB28, was able to have antitumor activity and to enhance anthracycline efficacy in two human breast cancer cell lines, MCF7 and MCF7 ADR, both characterized by significant sigma(2) receptor expression, by high and low sigma(1) receptor expression, and low and high P-gp expression, respectively. In both cell lines, PB28 showed high sigma(2) receptor affinity and low sigma(1) receptor affinity; furthermore, it inhibited cell growth with a clear effect at 48 hours (IC(50) in nanomolar range), a consistent time exposure-independent increase of G(0)-G(1)-phase fraction (of approximately 20% of both cell lines) and caspase-independent apoptosis (15% increased after 1-day drug exposure). PB28 also reduced P-gp expression in a concentration- and time-dependent manner ( approximately 60% in MCF7 and 90% in MCF7 ADR).
Reference: Mol Cancer Ther. 2006 Jul;5(7):1807-16. https://pubmed.ncbi.nlm.nih.gov/16891467/
In vivo activity:
This study found that tumours derived from PB28 treatment group grew at a slower rate (p < 0.0001) and were lighter than tumours derived from control group (p = 0.00286), and Ki‐67 presented a weaker staining (Figure 4). Furthermore, not surprisingly, images of gross specimens and HE staining, PB28 significantly reduced the number and volume of lung metastatic nodules (p < 0.0001) (Figure 5). The above results were consistent with the findings in vitro, implicating TMEM97 as a candidate tumour suppressor in renal cancer.
Reference: J Cell Mol Med. 2021 Dec;25(24):11244-11256. https://pubmed.ncbi.nlm.nih.gov/34783163/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
5.0 |
11.27 |
| Water |
9.0 |
20.29 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
443.50
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Cassano G, Gasparre G, Niso M, Contino M, Scalera V, Colabufo NA. F281, synthetic agonist of the sigma-2 receptor, induces Ca2+ efflux from the endoplasmic reticulum and mitochondria in SK-N-SH cells. Cell Calcium. 2009 Apr;45(4):340-5. doi: 10.1016/j.ceca.2008.12.005. Epub 2009 Feb 1. PMID: 19187959.
2. Azzariti A, Colabufo NA, Berardi F, Porcelli L, Niso M, Simone GM, Perrone R, Paradiso A. Cyclohexylpiperazine derivative PB28, a sigma2 agonist and sigma1 antagonist receptor, inhibits cell growth, modulates P-glycoprotein, and synergizes with anthracyclines in breast cancer. Mol Cancer Ther. 2006 Jul;5(7):1807-16. doi: 10.1158/1535-7163.MCT-05-0402. PMID: 16891467.
3. Zhan B, Zhang Z, Piao C, Dong X, Du Y, Kong C, Jiang Y. The Sigma-2 Receptor/TMEM97 Agonist PB28 Suppresses Cell Proliferation and Invasion by Regulating the PI3K-AKT-mTOR Signalling Pathway in Renal Cancer. J Cell Mol Med. 2021 Dec;25(24):11244-11256. doi: 10.1111/jcmm.17047. Epub 2021 Nov 16. PMID: 34783163; PMCID: PMC8650047.
4. Liu X, Fu Y, Yang H, Mavlyutov T, Li J, McCurdy CR, Guo LW, Pattnaik BR. Potential independent action of sigma receptor ligands through inhibition of the Kv2.1 channel. Oncotarget. 2017 Jul 26;8(35):59345-59358. doi: 10.18632/oncotarget.19581. PMID: 28938641; PMCID: PMC5601737.
In vitro protocol:
1. Cassano G, Gasparre G, Niso M, Contino M, Scalera V, Colabufo NA. F281, synthetic agonist of the sigma-2 receptor, induces Ca2+ efflux from the endoplasmic reticulum and mitochondria in SK-N-SH cells. Cell Calcium. 2009 Apr;45(4):340-5. doi: 10.1016/j.ceca.2008.12.005. Epub 2009 Feb 1. PMID: 19187959.
2. Azzariti A, Colabufo NA, Berardi F, Porcelli L, Niso M, Simone GM, Perrone R, Paradiso A. Cyclohexylpiperazine derivative PB28, a sigma2 agonist and sigma1 antagonist receptor, inhibits cell growth, modulates P-glycoprotein, and synergizes with anthracyclines in breast cancer. Mol Cancer Ther. 2006 Jul;5(7):1807-16. doi: 10.1158/1535-7163.MCT-05-0402. PMID: 16891467.
In vivo protocol:
1. Zhan B, Zhang Z, Piao C, Dong X, Du Y, Kong C, Jiang Y. The Sigma-2 Receptor/TMEM97 Agonist PB28 Suppresses Cell Proliferation and Invasion by Regulating the PI3K-AKT-mTOR Signalling Pathway in Renal Cancer. J Cell Mol Med. 2021 Dec;25(24):11244-11256. doi: 10.1111/jcmm.17047. Epub 2021 Nov 16. PMID: 34783163; PMCID: PMC8650047.
2. Liu X, Fu Y, Yang H, Mavlyutov T, Li J, McCurdy CR, Guo LW, Pattnaik BR. Potential independent action of sigma receptor ligands through inhibition of the Kv2.1 channel. Oncotarget. 2017 Jul 26;8(35):59345-59358. doi: 10.18632/oncotarget.19581. PMID: 28938641; PMCID: PMC5601737.
1: 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. Mol Cancer Ther. 2006;5(7):1807-1816. doi:10.1158/1535-7163.MCT-05-0402
2: 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. Published 2017 Jan 13. doi:10.1186/s12885-016-3040-4
3: Colabufo NA, Berardi F, Contino M, Perrone R, Tortorella V. A new method for evaluating sigma(2) ligand activity in the isolated guinea-pig bladder. Naunyn Schmiedebergs Arch Pharmacol. 2003;368(2):106-112. doi:10.1007/s00210-003-0777-5
4: 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). J Med Chem. 2009;52(23):7817-7828. doi:10.1021/jm9007505
5: Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. Preprint. bioRxiv. 2020;2020.03.22.002386. Published 2020 Mar 22. doi:10.1101/2020.03.22.002386
