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Purity: ≥98%
Pifithrin-β (also known as QB102 and Cyclic-Pifithrin-α) is a novel and potent p53 inhibitor with an IC50 of 23 μM. It is an analog of Pifithrin-α that is cell-permeable but has greater stability and less cytotoxicity. Pifithrin-β has neuroprotective properties by reversing the effects of Alzheimer peptide non-amyloid component in human SH-SY5Y cells. The TP53 gene in humans is responsible for encoding the protein p53. 53 KD is the molecular weight of p53. The p53 gene controls the cell cycle, acting as a tumor suppressor and preventing the development of cancer. Through the activation of DNA repair proteins, cell growth arrest through holding the cell cycle, and induction of apoptosis, the p53 plays a critical role in apoptosis, the inhibition of angiogenesis, and genomic stability. DNA damage, osmotic shock, oxidative stress, and a variety of other stressors can all cause p53 to become activated. By binding to DNA, including p21, activated p53 activates the expression of numerous genes.
| Targets |
p53 (IC50 = 23 μM)
Tumor protein p53 (p53): In HCT116 p53⁺/⁺ cells transfected with a p53-dependent luciferase reporter plasmid, the half-maximal effective concentration (EC₅₀) for inhibiting p53-mediated transcriptional activity was approximately 1.2 μM [2] - Aryl hydrocarbon receptor (AhR): In HepG2 cells transfected with an AhR-dependent luciferase reporter plasmid, the EC₅₀ for activating AhR-mediated transcriptional activity was approximately 0.8 μM [2] - Non-β-amyloid component (NAC)-induced cytotoxic signaling pathways: Pifithrin-β counteracts NAC-induced cell damage in SH-SY5Y cells; no specific IC₅₀ or EC₅₀ values for individual targets in this pathway were reported [3] |
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| ln Vitro |
Pifithrin-α, an inhibitor of the p53 protein, is thought to be a promising drug for the treatment of cancer and neurodegenerative diseases. In culture medium, Pifithrin-α is very unstable and quickly transforms into its condensation product, pifithrin-β (PFT), the N-acetyl derivative[2]. Viability testing reveals that pretreatments with 1 and 10 μM pifithrin-β exert neuroprotective effects after 24 hours[3].
Inhibition of p53-mediated transcriptional activity: In HCT116 p53⁺/⁺ cells treated with Pifithrin-β (0.1-10 μM), p53-dependent luciferase reporter activity was dose-dependently reduced. At 10 μM, the activity was inhibited by ~75% compared to the vehicle control (without Pifithrin-β). This inhibition was p53-specific, as no significant effect was observed in HCT116 p53⁻/⁻ cells (lacking functional p53) [2] - Activation of AhR signaling pathway: In HepG2 cells treated with Pifithrin-β (0.01-5 μM), AhR-dependent luciferase reporter activity was dose-dependently increased, with an EC₅₀ of ~0.8 μM. At 5 μM, the activity was ~4.2-fold higher than the control. Additionally, Pifithrin-β (1-10 μM) upregulated the mRNA expression of AhR target genes (e.g., CYP1A1, CYP1B1) in HepG2 cells (detected via RT-PCR), with CYP1A1 mRNA levels increased by ~3.8-fold at 10 μM [2] - Counteraction of NAC-induced cytotoxicity in SH-SY5Y cells: In human neuroblastoma SH-SY5Y cells treated with NAC (20 μM, an Alzheimer’s disease-related toxic peptide) and Pifithrin-β (1-20 μM): - Cell viability (measured via MTT assay) was dose-dependently restored: at 10 μM, viability increased from ~45% (NAC alone) to ~80% (vs. untreated control); - Apoptosis (detected via Annexin V-FITC/PI staining) was reduced: the apoptotic rate decreased from ~38% (NAC alone) to ~12% at 10 μM Pifithrin-β; - Mitochondrial membrane potential (measured via JC-1 staining) was recovered: the ratio of red/green fluorescence (indicating healthy mitochondria) increased from ~0.3 (NAC alone) to ~0.8 at 10 μM Pifithrin-β [3] |
| Enzyme Assay |
p53-dependent luciferase reporter assay: HCT116 p53⁺/⁺ cells and HCT116 p53⁻/⁻ cells were seeded in 96-well plates and transfected with a p53-responsive luciferase reporter plasmid (containing p53-binding elements) and a Renilla luciferase plasmid (for normalization) using a transfection reagent. After 24 hours of transfection, cells were treated with Pifithrin-β (0.1-10 μM) or vehicle. Following 16 hours of incubation, cells were lysed, and luciferase activity was measured using a dual-luciferase reporter assay system. The relative luciferase activity (firefly/Renilla) was calculated to assess p53 transcriptional activity [2]
- AhR-dependent luciferase reporter assay: HepG2 cells were seeded in 96-well plates and transfected with an AhR-responsive luciferase reporter plasmid (containing AhR-binding elements) and a Renilla luciferase plasmid. After 24 hours, cells were treated with Pifithrin-β (0.01-5 μM) or vehicle. Following 24 hours of incubation, cells were lysed, and dual-luciferase activity was measured. The relative luciferase activity was used to evaluate AhR activation [2] |
| Cell Assay |
RT-PCR for AhR target gene expression: HepG2 cells were seeded in 6-well plates and treated with Pifithrin-β (1-10 μM) or vehicle for 24 hours. Total RNA was extracted from cells using an RNA isolation reagent, and complementary DNA (cDNA) was synthesized via reverse transcription. RT-PCR was performed using gene-specific primers for CYP1A1, CYP1B1, and GAPDH (housekeeping gene). The relative mRNA expression levels were calculated using the 2⁻ΔΔCt method, with GAPDH as the normalization control [2]
- MTT assay for NAC-induced cytotoxicity: SH-SY5Y cells were seeded in 96-well plates (5×10³ cells/well) and cultured overnight. Cells were pre-treated with Pifithrin-β (1-20 μM) for 2 hours, then co-treated with NAC (20 μM) for 48 hours. MTT reagent (5 mg/mL) was added to each well, and cells were incubated at 37°C for 4 hours. The supernatant was removed, and formazan crystals were dissolved in DMSO. Absorbance at 570 nm was measured using a microplate reader, and cell viability was expressed as a percentage of the untreated control [3] - Annexin V-FITC/PI apoptosis assay: SH-SY5Y cells were treated as described in the MTT assay. After treatment, cells were trypsinized, washed with PBS, and stained with Annexin V-FITC and propidium iodide (PI) for 15 minutes in the dark. Apoptotic cells (Annexin V⁺/PI⁻ and Annexin V⁺/PI⁺) were analyzed using a flow cytometer, and the apoptotic rate was calculated [3] - JC-1 mitochondrial membrane potential assay: SH-SY5Y cells were treated as above, then incubated with JC-1 dye (10 μM) at 37°C for 20 minutes. Cells were washed with PBS, and fluorescence intensity (red: healthy mitochondria, green: damaged mitochondria) was measured using a fluorescence microplate reader. The red/green fluorescence ratio was calculated to assess mitochondrial membrane potential [3] |
| Toxicity/Toxicokinetics |
In vitro cytotoxicity: In HCT116 p53⁺/⁺, HCT116 p53⁻/⁻, HepG2 and SH-SY5Y cells, Pifithrin-β (at concentrations up to 20 μM, treated for 48 hours) did not cause significant cytotoxicity (MTT assay: cell viability >90%, compared to untreated control group) [2][3] - Data on median lethal dose (LD₅₀), hepatotoxicity, nephrotoxicity, drug interactions or plasma protein binding of Pifithrin-β were not reported in [1], [2] or [3].
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| References |
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| Additional Infomation |
2-(4-Methylphenyl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole belongs to the imidazole class of compounds.
Pifithrin-β (also known as QB-102 or cyclic Pifithrin-α) is a condensation product of Pifithrin-α, a known p53 inhibitor. Unlike Pifithrin-α, Pifithrin-β has dual activity: inhibiting p53 function and activating the AhR signaling pathway [2]. - The neuroprotective effect of Pifithrin-β in SH-SY5Y cells (against NAC-induced damage) is related to its p53 inhibitory activity, as NAC-induced cytotoxicity is partly mediated by p53-dependent apoptosis and mitochondrial dysfunction. Pifithrin-β restores cell survival by blocking p53-mediated pro-apoptotic signaling pathways [3] - Pifithrin-β is a potential tool compound for studying p53-AhR interactions and may have the potential to treat neurodegenerative diseases such as Alzheimer's disease by targeting p53-dependent cell death pathways [2][3] |
| Molecular Formula |
C₁₆H₁₆N₂S
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| Molecular Weight |
268.38
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| Exact Mass |
268.103
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| Elemental Analysis |
C, 55.02; H, 4.91; Br, 22.88; N, 8.02; S, 9.18
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| CAS # |
60477-34-1
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| Related CAS # |
Pifithrin-β hydrobromide;511296-88-1
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| PubChem CID |
443278
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| Appearance |
Solid powder
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| LogP |
4.25
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
327
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| Defined Atom Stereocenter Count |
0
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| SMILES |
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 |
IMUKUMUNZJILCG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H16N2S/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
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| Chemical Name |
2-(4-methylphenyl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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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)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。
注射用配方
注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)(IP/IV/IM/SC等) *生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。 注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline) 注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil) 示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。 View More
注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)] 口服配方
口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠) 口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素) 示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。 View More
口服配方 3: 溶解于 PEG400 (聚乙二醇400) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7261 mL | 18.6303 mL | 37.2606 mL | |
| 5 mM | 0.7452 mL | 3.7261 mL | 7.4521 mL | |
| 10 mM | 0.3726 mL | 1.8630 mL | 3.7261 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 NAC increased the level of p53 target gene transcription.ACS Chem Neurosci. 2014 May 21; 5(5): 390–399. |
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 NAC treatment induced cell cycle arrest.ACS Chem Neurosci. 2014 May 21; 5(5): 390–399. |
 NAC induced apoptotic cell death.ACS Chem Neurosci. 2014 May 21; 5(5): 390–399. |
 Cytotoxic effects of the tested compounds and pifithrin-β at 1 (A) and 10 μM (B) on SH-SY5Y cells.ACS Chem Neurosci. 2014 May 21; 5(5): 390–399. |
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 Neuroprotective effects of compounds4,12, and19.ACS Chem Neurosci. 2014 May 21; 5(5): 390–399. |
 (A) Concentration–response curves of compound12and pifithrin-β.ACS Chem Neurosci. 2014 May 21; 5(5): 3 |
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