| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
IC50: 3 nM (PrPC in ScN2a and F3 cells)[1]
TCS PrP Inhibitor 13 targets the cellular prion protein (PrPC) and inhibits the accumulation of its protease-resistant form (PrP-res). It is a potent inhibitor of PrP-res accumulation, with an IC50 of 3 nM in prion-infected mouse neuroblastoma (N2a) cell lines. By inhibiting PrP-res formation, it may prevent the propagation of prion diseases and induce apoptosis in prion-infected cells. |
|---|---|
| ln Vitro |
TCS PrP Inhibitor 13 (0~500 μM; Schwannoma cells) dramatically raises the expression of cleaved caspase-3 while dramatically lowering levels of total ERK1/2, pAKT, total FAK, Cyclin D1, and PrPC. The overall number of cells and the number of proliferating, Ki67-positive cells are both dramatically decreased by TCS PrP Inhibitor 13 (Schwannoma cells)[2].
In vitro, TCS PrP Inhibitor 13 (0–500 μM) significantly reduces the levels of total ERK1/2, pAKT, total FAK, Cyclin D1, and PrPC in Schwannoma cells. It also significantly increases the expression of cleaved caspase-3 and reduces the number of Ki67-positive proliferating cells and total cell number. These effects are consistent with the induction of apoptosis and cell cycle arrest. |
| ln Vivo |
In vivo data for TCS PrP Inhibitor 13 are limited. As an antiprion agent, it is expected to have potential in treating prion diseases. However, specific in vivo studies have not been detailed in the available literature. Further research is needed to evaluate its efficacy and safety in animal models of prion infection.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for TCS PrP Inhibitor 13 typically involves assessing its ability to inhibit PrP-res accumulation in prion-infected cells. This is measured using cell-based assays, such as Western blotting, to quantify the levels of PrP-res. The compound's IC50 of 3 nM was determined in ScN2a and F3 cell lines. These assays are crucial for evaluating the antiprion activity of the compound.
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| Cell Assay |
To find effective antiprion compounds, researchers synthesized and evaluated various pyrazolone derivatives. Seven of 19 compounds showed inhibition of PrP-res accumulation and the remarkably active compound 13 showed an IC50 value of 3 nM in both ScN2a and F3 cell lines. Findings from studies on physicochemical and biochemical properties suggest that the action mechanism of these compounds does not correlate with any antioxidant activities, any of hydroxyl radical scavenging activities, or any SOD-like activities.[1]
Cellular assays for TCS PrP Inhibitor 13 are performed using prion-infected mouse neuroblastoma (N2a) cell lines, such as ScN2a and F3 cells. Cells are treated with varying concentrations of the compound, and the accumulation of PrP-res is measured. The IC50 value of 3 nM is determined from these dose-response experiments. Apoptosis is assessed by measuring cleaved caspase-3 levels. |
| Animal Protocol |
In vivo animal protocols for TCS PrP Inhibitor 13 are not available in the literature. As an antiprion agent, it would typically be evaluated in mouse models of prion disease. However, such studies have not been reported. The compound is currently used primarily for in vitro research to study prion biology and screen for antiprion compounds.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of TCS PrP Inhibitor 13 have not been characterized. It is a small molecule with a molecular weight of 281.27. The compound is typically dissolved in DMSO for in vitro studies. In vivo formulations may include 10% DMSO, 40% PEG300, and 5% Tween 80. Further studies are needed to determine its ADME profile.
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| Toxicity/Toxicokinetics |
Toxicity data for TCS PrP Inhibitor 13 are limited. It induces apoptosis in Schwannoma cells, indicating some cytotoxic potential. Comprehensive toxicological studies have not been conducted. The compound is intended for research use only and is not approved for human therapeutic use.
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| References |
[1]. Kimata A, et al. New series of antiprion compounds: pyrazolone derivatives have the potent activity of inhibiting protease-resistant prion protein accumulation [published correction appears in J Med Chem. 2008 Mar 13;51(5):1503]. J Med Chem. 2007;50(21):5053-5056.
[2]. Provenzano L, et al. Cellular prion protein (PrPC) in the development of Merlin-deficient tumours. Oncogene. 2017;36(44):6132-6142. |
| Additional Infomation |
Loss-of-function mutations in the neurofibromatosis type 2 (NF2) gene encode the tumor suppressor gene Merlin, which can lead to various neurological tumors, such as schwannomas, meningiomas, and ependymomas. These tumors may occur sporadically or as part of the hereditary neurofibromatosis type 2 (NF2). Current treatment options are limited to (radio)surgery, with no targeted drug therapies available. NF2 gene mutations and/or Merlin inactivation are also seen in other cancers, including certain mesotheliomas, breast cancer, colorectal cancer, melanoma, and glioblastoma. To investigate the relationship between Merlin deficiency and tumorigenesis, we established an in vitro model containing human primary schwannomas, the most common Merlin-deficient tumor and a hallmark tumor of NF2. Using this model, we found increased expression of cytokinin (PrPC) in schwannomas and tissues. Furthermore, significant overexpression of PrPC was observed in both the human Merlin-deficient mesothelioma cell line TRA and the human Merlin-deficient meningioma. PrPC promotes the proliferation, cell-matrix adhesion, and survival of schwannomas through the 37/67 kDa non-integrin laminin receptor (LR/37/67 kDa) and its downstream ERK1/2, PI3K/AKT, and FAK signaling pathways. PrPC protein can also be released in large quantities from schwannomas in the form of exosomes and free peptides, suggesting that it may function in an autocrine and/or paracrine manner. We believe that PrPC and its interacting protein LR/37/67 kDa may be potential therapeutic targets for schwannomas and other Merlin-deficient tumors. [2]
TCS PrP Inhibitor 13 is also known as 5-(4-Nitrophenyl)-2-Phenyl-4H-Pyrazol-3-One. It is a potent antiprion agent that inhibits PrP-res accumulation with an IC50 of 3 nM. The compound is not currently in clinical trials and is used primarily as a research tool for studying prion diseases. |
| Molecular Formula |
C15H11N3O3
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|---|---|
| Molecular Weight |
281.27
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| Exact Mass |
281.08
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| Elemental Analysis |
C, 64.05; H, 3.94; N, 14.94; O, 17.06
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| CAS # |
34320-83-7
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| PubChem CID |
2750328
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| Appearance |
White to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
445.1±47.0 °C at 760 mmHg
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| Flash Point |
223.0±29.3 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.674
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| LogP |
1.92
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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 |
2
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| Heavy Atom Count |
21
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| Complexity |
444
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1CC(C2C=CC(=CC=2)[N+](=O)[O-])=NN1C1C=CC=CC=1
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| InChi Key |
FDAVFKZPGQEGDX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H11N3O3/c19-15-10-14(11-6-8-13(9-7-11)18(20)21)16-17(15)12-4-2-1-3-5-12/h1-9H,10H2
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| Chemical Name |
5-(4-nitrophenyl)-2-phenyl-4H-pyrazol-3-one
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| Synonyms |
TCS PRP INHIBITOR 13; 34320-83-7; 5-(4-nitrophenyl)-2-phenyl-4H-pyrazol-3-one; 3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-5(4H)-one; 3-(4-Nitrophenyl)-1-phenyl-2-pyrazolin-5-one; 2,4-DIHYDRO-5-(4-NITROPHENYL)-2-PHENYL-3H-PYRAZOL-3-ONE; 5-(4-nitrophenyl)-2-phenyl-2,4-dihydro-3H-pyrazol-3-one; ST51035799;
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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 |
| 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) |
DMSO : 100 mg/mL (355.53 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5553 mL | 17.7765 mL | 35.5530 mL | |
| 5 mM | 0.7111 mL | 3.5553 mL | 7.1106 mL | |
| 10 mM | 0.3555 mL | 1.7777 mL | 3.5553 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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