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Pifithrin-β HBr (QB-102; Cyclic-Pifithrin-α), the hydrobromide salt of Pifithrin-β, is a potent p53 inhibitor (IC50 of 23 μM) and a cell-permeable Cyclized analog of Pifithrin-α with higher stability and reduced cytotoxicity. Neuroprotective properties of Pifithrin-β HBr.
Physicochemical Properties
| Molecular Formula | C16H17BRN2S | |
| Molecular Weight | 349.29 | |
| Exact Mass | 348.029 | |
| Elemental Analysis | C, 55.02; H, 4.91; Br, 22.88; N, 8.02; S, 9.18 | |
| CAS # | 511296-88-1 | |
| Related CAS # | Pifithrin-β;60477-34-1 | |
| PubChem CID | 11515812 | |
| Appearance | White to off-white solid powder | |
| LogP | 5.208 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 2 | |
| Rotatable Bond Count | 1 | |
| Heavy Atom Count | 20 | |
| Complexity | 327 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | Br[H].S1C2=NC(C3C([H])=C([H])C(C([H])([H])[H])=C([H])C=3[H])=C([H])N2C2=C1C([H])([H])C([H])([H])C([H])([H])C2([H])[H] |
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| InChi Key | SGNCOAOESGSEOP-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C16H16N2S.BrH/c1-11-6-8-12(9-7-11)13-10-18-14-4-2-3-5-15(14)19-16(18)17-13;/h6-10H,2-5H2,1H3;1H | |
| Chemical Name | 2-(4-methylphenyl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole;hydrobromide | |
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| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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 | p53 (IC50 = 23 μM) |
| ln Vitro | Pifithrin-α hydrobromide (PFT β hydrobromide), an inhibitor of the p53 protein, is thought to be a promising drug candidate for the treatment of cancer and neurodegenerative diseases. The N-acetyl derivative of pifithrin, Pifithrin-α, is produced quickly from the extremely unstable precursor pifithrin-β, which is very unstable in culture medium[2]. The viability assay demonstrates, after 24 hours, that pretreatments with 1 and 10 μM pifithrin-β exert neuroprotective effects[3]. |
| Cell Assay | For 24 hours, the H460 and IGROV-1 cell lines were subjected to either PFT or paclitaxel treatment alone or in combination. Following a PBS wash, the cells were fixed for 30 minutes in 2% paraformaldehyde before being permeabilized for 20 minutes at 20°C in ice-cold methanol. Anti-p53 antibody was incubated for 1 hour at room temperature after blocking with PBA (PBS containing 1% bovine serum albumin), and then for 1 hour with Alexa Fluor 488 goat antimouse IgG secondary antibody. Confocal microscopy was used to view and examine images. |
| References |
[1]. Synthesis and biological evaluation of imidazolo[2,1-b]benzothiazole derivatives, as potential p53 inhibitors. Bioorg Med Chem. 2011 Mar 1;19(5):1649-57. [2]. Biological and chemical studies on aryl hydrocarbon receptor induction by the p53 inhibitor pifithrin-α and its condensation productpifithrin-β. Life Sci. 2011 Apr 25;88(17-18):774-83. [3]. p53 functional inhibitors behaving like pifithrin-β counteract the Alzheimer peptide non-β-amyloid component effects in human SH-SY5Y cells. ACS Chem Neurosci. 2014 May 21;5(5):390-9. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (2.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 1 mg/mL (2.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8630 mL | 14.3148 mL | 28.6295 mL | |
| 5 mM | 0.5726 mL | 2.8630 mL | 5.7259 mL | |
| 10 mM | 0.2863 mL | 1.4315 mL | 2.8630 mL |