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| Targets |
Pifithrin-α, p-Nitro, Cyclic primarily targets p53, a tumor suppressor protein that plays a critical role in regulating cell cycle arrest, apoptosis, and DNA repair. It acts as a p53 posttranscriptional activity inhibitor, meaning it inhibits p53 function at the posttranscriptional level without preventing its phosphorylation on the S15 residue. By inhibiting p53, the compound protects cells from p53-induced cell death, making it a valuable tool for studying p53-mediated apoptosis and for protecting cells from DNA damage-induced cell death.
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| ln Vitro |
At concentrations one order of magnitude lower than PFT-α, Pifithrin-α, p-Nitro, Cyclic (PFN-α) efficiently inhibits p53-triggered cell death and p21/WAF1 expression in cortical neurons exposed to etoposide[1].
In vitro, Pifithrin-α, p-Nitro, Cyclic is one order of magnitude more active than Pifithrin-α in protecting cortical neurons exposed to etoposide (ED50 = 30 nM). It significantly inhibits p53-induced cell death and p21/WAF1 expression in cortical neurons exposed to etoposide, requiring concentrations an order of magnitude lower than PFT-α. The compound behaves as a p53 posttranscriptional activity inhibitor and does not prevent p53 phosphorylation on the S15 residue. |
| ln Vivo |
Pifithrin-α injection intraocularly at a concentration of 6 μM marginally enhanced the survival of retinal ganglion cells (RGCs), but not at a concentration of 0.06 μM. Even at a concentration of 6 μM, pifithrin-α, p-Nitro, Cyclic (PFN-α) is ineffective in vivo [1]. When incubated under biological conditions, Pifithrin-α, p-Nitro, Cyclic has a half-life (t1/2) of six hours [1].
In vivo, Pifithrin-α, p-Nitro, Cyclic has been studied for its ability to protect cells from p53-mediated apoptosis. As a cell-permeable p53 inhibitor with enhanced potency and longer half-life compared to Pifithrin-α, it has potential applications in protecting normal tissues from the toxic effects of chemotherapy and radiation. However, specific in vivo efficacy data, including dosing regimens and animal models, are not extensively detailed in the available literature. Further studies are needed to fully characterize its in vivo pharmacological profile. |
| Enzyme Assay |
Cell-free assays for Pifithrin-α, p-Nitro, Cyclic involve studying its interaction with p53 and its effects on p53 transcriptional activity. The compound's ability to inhibit p53-mediated transcription can be assessed using cell-free transcription assays with purified p53 protein and DNA templates. Binding assays such as surface plasmon resonance (SPR) can be used to study the compound's interaction with p53. The compound's chemical purity and identity are confirmed by HPLC and NMR analysis.
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| Cell Assay |
In vitro cellular assays for Pifithrin-α, p-Nitro, Cyclic typically involve treating cortical neurons or other cell types with etoposide or other DNA-damaging agents to induce p53-mediated cell death. Cells are pre-treated with various concentrations of the compound (at concentrations an order of magnitude lower than PFT-α). Cell viability is assessed using MTT or other standard assays. p21/WAF1 expression is measured by western blotting or qPCR to assess p53 transcriptional activity. Apoptosis is evaluated using Annexin V/PI staining and caspase activity assays.
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| Animal Protocol |
In vivo animal studies for Pifithrin-α, p-Nitro, Cyclic are conducted in models of chemotherapy-induced toxicity or radiation injury. The compound is administered via various routes including intraperitoneal or intravenous injection. Tissue damage is assessed by histopathology and biochemical markers. Survival studies evaluate the protective effect of the compound. However, specific dosing regimens and experimental protocols are not extensively documented in the available literature. Standard protocols for evaluating p53 inhibitors would typically be employed.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Pifithrin-α, p-Nitro, Cyclic include a molecular weight of 307.30 g/mol and molecular formula C16H13N3O3. The compound is cell-permeable and has a longer half-life than Pifithrin-α. It is typically stored at appropriate conditions as a research reagent. Detailed ADME parameters such as half-life, Cmax, and AUC are not extensively reported in the available literature. The compound is typically handled as a solid and stored at appropriate conditions.
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| Toxicity/Toxicokinetics |
The toxicity profile of Pifithrin-α, p-Nitro, Cyclic has not been extensively characterized in published literature. As a p53 inhibitor, potential toxicities may include effects on normal cellular functions and increased cancer risk. The compound is intended for research use only and not for therapeutic applications in humans. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
Pifithrin-α, p-Nitro, Cyclic is a cell-permeable p53 inhibitor that is one order of magnitude more potent and has a longer half-life than Pifithrin-α. It significantly inhibits p53-induced cell death and p21/WAF1 expression in cortical neurons exposed to etoposide at concentrations an order of magnitude lower than PFT-α (ED50 = 30 nM). The compound is a p53 posttranscriptional activity inhibitor. It is a research tool for studying p53-mediated apoptosis and protecting cells from DNA damage.
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| Molecular Formula |
C15H13N3O2S
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| Molecular Weight |
299.3476
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| Exact Mass |
299.072
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| CAS # |
60477-38-5
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| PubChem CID |
4587369
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.780
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| LogP |
5.63
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
21
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| Complexity |
408
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CCC2=C(C1)N3C=C(N=C3S2)C4=CC=C(C=C4)[N+](=O)[O-]
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| InChi Key |
XMFNSEDROOHGBY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13N3O2S/c19-18(20)11-7-5-10(6-8-11)12-9-17-13-3-1-2-4-14(13)21-15(17)16-12/h5-9H,1-4H2
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| Chemical Name |
2-(4-nitrophenyl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMF : 12.5 mg/mL (~41.76 mM)
DMSO : ~5 mg/mL (~16.70 mM) |
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3406 mL | 16.7029 mL | 33.4057 mL | |
| 5 mM | 0.6681 mL | 3.3406 mL | 6.6811 mL | |
| 10 mM | 0.3341 mL | 1.6703 mL | 3.3406 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.
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