| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary targets of Fe-TMPyP are peroxynitrite (ONOO⁻), a highly reactive nitrogen species, and the prion protein PrP. As a peroxynitrite decomposition catalyst, Fe-TMPyP targets this potent oxidant to mitigate its damaging effects on cells and tissues, which are implicated in a wide range of pathological conditions including neuroinflammation, ischemia-reperfusion injury, and various neurodegenerative disorders. By catalytically breaking down peroxynitrite, the compound helps to restore the balance of the cellular redox environment. Additionally, Fe-TMPyP has a unique ability to bind to the prion protein PrP, inhibiting its misfolding into the pathogenic isoform that is characteristic of prion diseases like Creutzfeldt-Jakob disease. This interaction with PrP highlights the compound's utility in studying the molecular basis of protein misfolding diseases. Therefore, Fe-TMPyP's targets are central to both oxidative stress and protein aggregation pathways.
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| ln Vitro |
Fe-TMPyP exhibits significant in vitro activity as a peroxynitrite decomposition catalyst, characterized by a high rate constant of 2.2 × 10⁶ M⁻¹s⁻¹ and a turnover number of 360 ± 170 s⁻¹. This indicates that the compound can rapidly and efficiently break down peroxynitrite, even at low concentrations. Its catalytic activity is superior to many other metalloporphyrins as it does not require exogenous reductants to complete the catalytic cycle, allowing for sustained activity. In cell-based systems, Fe-TMPyP effectively reduces nitrative stress by scavenging peroxynitrite and other reactive species, thereby decreasing the formation of nitrotyrosine, a marker of protein damage by reactive nitrogen species. Furthermore, its ability to bind to the prion protein PrP and inhibit its misfolding has been demonstrated in vitro, confirming its role as a tool for studying prion biology. This combination of potent catalytic activity and protein-binding properties makes Fe-TMPyP a versatile compound for in vitro research.
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| ln Vivo |
In vivo, Fe-TMPyP has demonstrated protective effects in several animal models. It has been shown to reduce chronic constrictive injury (CCI)-induced PARP hyperactivation and neuroinflammation in rats. This activity is linked to its function as a peroxynitrite scavenger, as it mitigates the nitrative stress that contributes to neuropathic pain and inflammation. By reducing nitrative stress, Fe-TMPyP improves functional, behavioral, and biochemical deficits in these models. Additionally, its ability to increase autophagy may contribute to its neuroprotective effects by promoting the clearance of damaged proteins and organelles. While its large molecular weight may pose challenges for crossing the blood-brain barrier, its oral bioavailability suggests it can reach systemic targets. These in vivo studies are crucial for understanding the therapeutic potential of Fe-TMPyP in conditions associated with oxidative and nitrative stress.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for Fe-TMPyP typically focus on its catalytic activity. To assess its peroxynitrite decomposition activity, a stopped-flow spectrophotometer is used. Fe-TMPyP is mixed with a known concentration of peroxynitrite in a phosphate buffer at physiological pH (7.4). The decomposition of peroxynitrite is monitored by following the decrease in its characteristic absorbance at 302 nm over time. By comparing the rate of decay in the presence of the catalyst to the spontaneous decay rate, the catalytic rate constant can be calculated. For its interaction with the prion protein, binding assays such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) can be employed. In these assays, the purified PrP protein is immobilized, and varying concentrations of Fe-TMPyP are flowed over the surface to measure binding affinity and kinetics. These non-cell assays are fundamental for characterizing the compound's primary biochemical activities.
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| Cell Assay |
In vitro cell-based experiments evaluate the biological effects of Fe-TMPyP in a cellular context. Cell lines, often neuronal or other cell types sensitive to oxidative stress, are treated with peroxynitrite donors or inflammatory stimuli (e.g., lipopolysaccharide, LPS) to induce nitrative stress. The cells are then co-treated with Fe-TMPyP to assess its protective effects. Key readouts include the measurement of nitrotyrosine levels by ELISA or immunoblotting, which serves as a marker for peroxynitrite-mediated protein damage. Cell viability and cytotoxicity are also assessed using standard assays like MTT or LDH release. Additionally, the compound's effect on autophagy can be studied by monitoring the conversion of LC3-I to LC3-II and the levels of p62 via Western blot. These experiments help to translate the compound's biochemical activity into functional cellular outcomes, such as protection against nitrative damage and the induction of cytoprotective autophagy.
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| Animal Protocol |
In vivo animal models are employed to study the therapeutic potential of Fe-TMPyP. One established model is the rat chronic constrictive injury (CCI) model of neuropathic pain. In this model, rats are subjected to surgery to induce a chronic constriction of the sciatic nerve, leading to neuroinflammation and pain-like behaviors. Fe-TMPyP is administered orally to evaluate its effects on these outcomes. After treatment, animals are assessed for behavioral signs of pain relief. At the end of the study, spinal cord or brain tissue is harvested to measure markers of neuroinflammation and oxidative stress, such as PARP hyperactivation and nitrotyrosine levels. Other models of inflammation or neurodegeneration may also be used. These studies are critical for determining the in vivo efficacy and bioavailability of Fe-TMPyP and for understanding its mechanism of action in a complex biological system.
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| ADME/Pharmacokinetics |
Fe-TMPyP has a molecular weight of 909.92 and is characterized as an orally bioactive compound. This indicates that it possesses sufficient stability and permeability to be absorbed from the gastrointestinal tract and reach systemic circulation. Detailed pharmacokinetic parameters such as half-life (t½), maximum plasma concentration (Cmax), bioavailability, and volume of distribution are not extensively reported in the public literature. However, its large size and cationic nature might limit its tissue penetration, including across the blood-brain barrier, although its in vivo efficacy in models of neuropathic pain suggests it can reach its targets in the central nervous system to some extent. Solubility data suggests it may dissolve in DMSO and other organic solvents. A complete ADME (Absorption, Distribution, Metabolism, Excretion) profile for Fe-TMPyP would require dedicated pharmacokinetic studies to fully characterize its behavior in living organisms.
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| Toxicity/Toxicokinetics |
Comprehensive toxicity data for Fe-TMPyP is not publicly available, as it is primarily used as a research compound and has not undergone the extensive toxicological evaluation required for drug development. As an iron-containing porphyrin, there is a potential for toxicity related to metal accumulation or the generation of oxidative stress at high concentrations. However, its function as a peroxynitrite scavenger suggests that at therapeutic doses, it may be protective against oxidative damage. The compound's safety profile would need to be established through a series of in vitro and in vivo toxicology studies, including assessments of genotoxicity, acute and chronic toxicity, and effects on major organ systems. For now, it is classified as a research tool and is not intended for human use, with all handling requiring standard laboratory safety precautions.
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| Additional Infomation |
Fe-TMPyP is a valuable and versatile research tool with applications spanning several fields of biomedical research. Its primary utility lies in studying the role of peroxynitrite-mediated nitrative stress in various pathological conditions, including neuroinflammation, neurodegenerative diseases (such as Alzheimer's and Parkinson's), and pain. Its ability to bind to the prion protein PrP and inhibit misfolding also makes it a unique probe for studying the molecular mechanisms of prion diseases. The compound has not advanced to clinical trials and does not have FDA approval for any therapeutic indication. It remains a fundamental tool in academic and pharmaceutical research laboratories for dissecting the complex signaling pathways involved in oxidative stress and protein misfolding.
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| Molecular Formula |
C44H36CL5FEN85
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|---|---|
| Molecular Weight |
909.92
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| Exact Mass |
714.509
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| CAS # |
133314-07-5
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| PubChem CID |
71433763
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| Appearance |
Brown to black solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.783
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| LogP |
7.88
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
53
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| Complexity |
1590
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C=CC(=C2C3=NC(=C(C4=CC=[N+](C)C=C4)C5=CC=C(C(=C6C=CC(=N6)C(=C7C=CC2=N7)C8=CC=[N+](C)C=C8)C9=CC=[N+](C)C=C9)[N-]5)C=C3)C=C1.[Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Fe+3]
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| InChi Key |
VTKLWUKNBYRMDP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C45H62N8/c1-46-21-13-29(14-22-46)41-33-5-7-35-42(30-15-23-47(2)24-16-30)37-9-11-39-44(32-19-27-49(4)28-20-32)40-12-10-38-43(31-17-25-48(3)26-18-31)36-8-6-34(41)51(36)45(50(33)35,52(37)39)53(38)40/h5,7,10,12,29-32,34,37H,6,8-9,11,13-28H2,1-4H3
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| Chemical Name |
7,12,17,24-tetrakis(1-methylpiperidin-4-yl)-2,22,23,25-tetrazaoctacyclo[11.9.1.11,8.13,21.02,6.016,23.018,22.011,25]pentacosa-3,5,7,12,14,16,21(24)-heptaene
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| Synonyms |
FeTMPyP; Fe TMPyP; Fe-TMPyP
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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) |
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
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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 | 1.0990 mL | 5.4950 mL | 10.9900 mL | |
| 5 mM | 0.2198 mL | 1.0990 mL | 2.1980 mL | |
| 10 mM | 0.1099 mL | 0.5495 mL | 1.0990 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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