Physicochemical Properties
| Molecular Formula | C24H38N2O |
| Molecular Weight | 370.57 |
| Exact Mass | 442.252 |
| CAS # | 172906-90-0 |
| Related CAS # | PB28 dihydrochloride;172907-03-8 |
| PubChem CID | 10474335 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 6.325 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 27 |
| Complexity | 428 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1(N2CCN(CCCC3C4C(=C(OC)C=CC=4)CCC3)CC2)CCCCC1 |
| InChi Key | PHRCDWVPTULQMT-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C24H38N2O/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 |
| Chemical Name | 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Ki: 0.68 nM (σ2 receptor); 0.38 nM (σ1 receptor)[4] |
| ln Vitro | For MCF7 and MCF7 ADR cells, PB28 (15–25 nM; 24-48 hours) treatment results in an accumulation in the G0-G1 phase that is independent of concentration and time[1]. Compared to σ1 receptor affinity (13.0 nM and 10.0 nM, respectively), PB28 has a greater σ2 receptor affinity expressed as Ki (0.28 nM and 0.17 nM in MCF7 and MCF7 ADR cells, respectively)[1]. After two days of therapy, PB28 suppresses the development of MCF7 and MCF7 ADR cells with IC50s of 25 nM and 15 nM, respectively[1]. PB28 uses a caspase-independent mechanism to cause apoptosis[1]. Moreover, PB28 decreases P-gp expression in MCF7 and MCF7 ADR in a concentration- and time-dependent manner (by about 60% and 90%, respectively)[1]. SK-N-SH human neuroblastoma cell lines and C6 rat glioma cell lines both exhibit cytotoxic and antiproliferative properties in response to PB28[1]. |
| ln Vivo | In Panc02 tumor burden mice, PB28 (10.7 mg/mL; intraperitoneal injection; daily; for two weeks; female C57BL/6 mice) therapy suppresses tumor growth. Mice who receive PB28 also have an advantage in survival[2]. |
| Cell Assay |
Cell Cycle Analysis[1] Cell Types: MCF7 and MCF7 ADR cells Tested Concentrations: 25 nM and 15 nM Incubation Duration: 24 hrs (hours), 48 hrs (hours) Experimental Results: demonstrated an accumulation in the G0-G1 phase for MCF7 and MCF7 ADR cells that were time and concentration independent. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 female mice (10 weeks old) injected with Panc02 cells[2] Doses: 10.7 mg/mL Route of Administration: intraperitoneal (ip)injection; daily; for two weeks Experimental Results: Inhibited tumor growth in Panc02 tumor burden mice. |
| References |
[1]. 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. [2]. 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. [3]. A New Method for Evaluating sigma(2) Ligand Activity in the Isolated Guinea-Pig Bladder. Naunyn Schmiedebergs Arch Pharmacol. 2003 Aug;368(2):106-12. [4]. 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 Dec 10. [5]. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. bioRxiv. 2020 Mar 22;2020.03.22.002386. |
| Additional Infomation | PB28 is a member of the class of tetralins that is tetralin that is substituted by 3-(4-cyclohexylpiperazin-1-yl)propyl and methoxy groups at positions 1 and 5, respectively. It is a sigma 2 (sigma2) receptor agonist (Ki = 0.68 nM) and exhibits antineoplastic and anti SARS-CoV-2 activities. It has a role as an anticoronaviral agent, an antineoplastic agent, an apoptosis inducer and a sigma-2 receptor agonist. It is an aromatic ether, a member of piperazines and a member of tetralins. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6985 mL | 13.4927 mL | 26.9855 mL | |
| 5 mM | 0.5397 mL | 2.6985 mL | 5.3971 mL | |
| 10 mM | 0.2699 mL | 1.3493 mL | 2.6985 mL |