| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg | |||
| 250mg | |||
| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
PARP ( IC50 = 110 nM ); PARP-2 ( IC50 = 86 nM ); PARP-1 ( IC50 = 110 nM )
PJ34 targets poly(ADP-ribose) polymerase (PARP) enzymes, particularly PARP-1 and PARP-2. PARP enzymes are involved in DNA damage repair and cell death signaling. By inhibiting PARP, PJ34 prevents the synthesis of poly(ADP-ribose) chains and reduces the consumption of NAD⁺. This helps to maintain cellular energy levels and reduce cell death. PARP inhibition also prevents the excessive poly(ADP-ribosyl)ation of proteins, which can lead to cellular dysfunction and death. The compound's inhibition of PARP1 and PARP2 is potent and specific, with IC₅₀ values of 110 nM and 86 nM, respectively. PJ34 has an EC₅₀ of 20 nM for PARP inhibition. Through these mechanisms, PJ34 exerts anti-inflammatory, cytoprotective, and neuroprotective effects. |
|---|---|
| ln Vitro |
The PARP enzyme activity is inhibited by PJ34, with an IC50 of 110±1.9 nM. The LDH neuroassay was utilized to assess PJ34's protective capabilities in PC12 cells in comparison to those of other PARP enzymes. Cell death in the concentration range of 10-7 to 10-5 M is also significantly and centrally inhibited by PJ34 treatment [1].
In vitro, PJ34 has been shown to inhibit PARP activity and reduce cell death in various cell models of oxidative stress and DNA damage. The compound prevents NAD⁺ depletion and excessive poly(ADP-ribosyl)ation, protecting cells from oxidative stress–induced injury. PJ34 reduces the production of pro-inflammatory cytokines and inhibits inflammatory signaling pathways. In cancer cell models, PARP inhibition by PJ34 can sensitize cells to DNA-damaging agents and induce cell death. The compound's effects on cell viability, apoptosis, and inflammatory marker expression can be assessed in various cell culture systems. |
| ln Vivo |
At dosages of 3.2 and 10 mg/kg, respectively, PJ34 was assessed for efficacy and comparability with other PARPs. A 33% reduction in skin lesions was shown when PJ34 was administered at a dose of 3.2 mg/kg; however, a 17% reduction was observed when the dose of 10 mg/kg was administered [1]. TNF-α mRNA levels were considerably reduced by 70% in animals when treated with PJ34 (25 mg/kg), and treated mice did not differ in these values from sham or naive animals. Treatment with PJ34 decreased ICAM-1 mRNA levels by 54% and E-selectin mRNA levels by 81% as compared to vehicle-treated treatments [2].
In vivo, PJ34 has been studied in animal models of ischemia-reperfusion injury, stroke, and neurodegenerative diseases. The compound has been shown to reduce infarct size, improve neurological outcomes, and reduce inflammation. In models of myocardial ischemia-reperfusion injury, PJ34 significantly decreased myocardial PARP activation and improved both cardiac dysfunction and vascular relaxation. The compound has demonstrated anti-inflammatory and cytoprotective effects in numerous preclinical models. PJ34 is typically administered intraperitoneally, with doses of 1.25-0.9% injected 15 minutes before ischemia and again 4 hours after the onset of ischemia. The compound's efficacy depends on the dose, route of administration, and the specific disease model. |
| Enzyme Assay |
Minor modifications are made to PARP activity in order to evaluate the inhibitory activity of PARP-1 or PARP-2 of FR247304, 3-AB, and PJ34. The PARP enzyme assay is performed in a final volume of 100 μL with the following contents: 50 mM Tris-HCl (pH 8.0), 25 mM MgCl2, 1 mM dithiothreitol, 10 μg activated salmon sperm DNA, 0.1 μCi of [adenylate-32P]NAD, 0.2 units of recombinant mouse PARP-2 for the PARP-2 assay, 0.1 units of recombinant human PARP for the PARP-1 assay, and different concentrations of FR261529 or 3-AB. After 15 minutes of room temperature (23°C) incubation, 200 μL of ice-cold 20% trichloroacetic acid (TCA) is added to the reaction mixture, and it is further incubated for 10 minutes at 4°C. The precipitate is moved to a GF/B filter, where it is cleaned three times using 70% ethanol and 10% TCA solution. Liquid scintillation counting is used to measure the radioactivity once the filter has dried.
For non-cellular enzyme assays, PJ34 can be tested for inhibition of PARP using standard enzyme activity assays. The enzyme is incubated with varying concentrations of the compound, and PARP activity is measured by the incorporation of radiolabeled NAD⁺ into poly(ADP-ribose) polymers or by using colorimetric or fluorometric methods. The IC₅₀ values for PARP1 and PARP2 inhibition can be determined. The compound's binding affinity to PARP can be assessed using surface plasmon resonance or other biophysical techniques. |
| Cell Assay |
PC12 cell cultures are maintained in Dulbecco's modified Eagle's medium, which is supplemented with 1% (v/v) of penicillin-streptomycin antibiotic mixture, 5% (v/v) of horse serum, and 5% (v/v) of fetal calf serum. At 37°C, cells are grown in an environment consisting of 95% air and 5% CO2. In every experiment, 96-well culture plates are seeded with 4×104 cells/well and left overnight for the cells to attach. Hydrogen peroxide-induced cytotoxicity is measured using an LDH assay kit to measure LDH release as a standard method of assessing cell viability. In summary, 20 μL of the medium from each well is collected 6 hours after the hydrogen peroxide exposure, and the LDH assay kit solution is added. The reaction is halted by adding 1 N HCl after 30 minutes of room temperature incubation, and absorbance is measured at 450 nm using a microplate reader.
For in vitro cell-based assays, cells are cultured and treated with PJ34 at various concentrations. PARP activity is measured by assessing the levels of poly(ADP-ribose) polymers using Western blotting or immunofluorescence. Cell viability is assessed using MTT or similar assays. Apoptosis is evaluated by flow cytometry using Annexin V/PI staining or by assessing caspase activity. Inflammatory marker expression is measured by ELISA or Western blotting. The compound's effects on NAD⁺ levels and cellular energy metabolism can also be assessed. |
| Animal Protocol |
Rats: Male Wistar rats, aged 9 to 10 weeks, weighing 274-380 g, are used for transient focal ischemia. The suspension of FR247304, PJ34, or 3-AB, which is suspended in 0.5% methylcellulose, is given intraperitoneally twice at 10 min before MCA occlusion and 10 min before recirculation. The doses for FR247304 are 10 and 32 mg/kg, 3.2 and 10 mg/kg, and 32 and 100 mg/kg, respectively. A correction of 2 mL/kg is made to the administration volume.
Mice: The mice used are male Swiss albino mice weighing 27–32 g. One hour prior to ischemia and again four hours after it starts, PJ34 (1.25, 12.5, or 25 mg/kg)—a PARP inhibitor—is dissolved in isotonic saline (NaCl, 0.9%) and injected intraperitoneally at a volume of 10 mL/kg. The vehicle (saline) is administered to sham animals and control ischemic mice. The studies also include naive animals.
For in vivo animal studies, PJ34 can be administered to animal models of disease. The compound is typically administered intraperitoneally. In models of ischemia-reperfusion injury, the compound is administered before and after the induction of ischemia. Tissue injury, infarct size, and functional outcomes are assessed. In models of neurodegeneration, the compound's effects on neuronal survival, inflammation, and behavioral outcomes are evaluated. Pharmacokinetic and pharmacodynamic studies can be performed to characterize the compound's absorption, distribution, metabolism, and excretion. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of PJ34 include a molecular weight of 295.34 and a molecular formula of C₁₇H₁₇N₃O₂. The compound is a cell-permeable small molecule. The compound is soluble in appropriate solvents such as DMSO. For in vivo administration, the compound can be formulated in various solvent systems. The compound should be stored under appropriate conditions. The powder is stable at -20°C for up to 3 years.
|
| Toxicity/Toxicokinetics |
PJ34 is generally well-tolerated in preclinical studies. The compound has demonstrated anti-inflammatory and cytoprotective effects in numerous preclinical models but is not approved for clinical use. The compound is intended for research use only and is not for human use.
|
| References |
|
| Additional Infomation |
PJ34 is a phenanthridine compound with the structure 5,6-dihydrophenanthridine, substituted at positions 2 and 6 with (N,N-dimethylglycyl)amino and carbonyl groups, respectively. It is a potent inhibitor of poly(ADP-ribose) polymerases PARP1 and PARP2 (IC50 values of 110 nM and 86 nM, respectively), and possesses anticancer, cardioprotective, and neuroprotective effects. It functions as an EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor, antitumor agent, apoptosis inducer, angiogenesis inhibitor, anti-atherosclerotic agent, cardioprotective agent, anti-inflammatory agent, and neuroprotective agent. It belongs to the phenanthridine, secondary amide, and tertiary amine classes. It is the conjugate base of PJ34(1+).
PJ34 is a potent inhibitor of poly(ADP-ribose) polymerases PARP1 and PARP2 (IC₅₀ of 110 nM and 86 nM, respectively). It is a member of the class of phenanthridines. By blocking PARP activity, PJ34 prevents NAD⁺ depletion and excessive poly(ADP-ribosyl)ation, protecting cells from oxidative stress–induced injury. The compound exhibits anti-cancer, cardioprotective, and neuroprotective properties. It is widely used as a research tool in studies of neuroprotection, inflammation, ischemia-reperfusion injury, and cancer biology. It is not currently approved for clinical use and is available only for research purposes. |
| Molecular Formula |
C17H17N3O2
|
|---|---|
| Molecular Weight |
295.3358
|
| Exact Mass |
295.132
|
| CAS # |
344458-19-1
|
| Related CAS # |
PJ34 hydrochloride;344458-15-7
|
| PubChem CID |
4858
|
| Appearance |
Light yellow to khaki solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
453.3±38.0 °C at 760 mmHg
|
| Flash Point |
227.9±26.8 °C
|
| Vapour Pressure |
0.0±1.1 mmHg at 25°C
|
| Index of Refraction |
1.649
|
| LogP |
0.57
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
22
|
| Complexity |
438
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
UYJZZVDLGDDTCL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H17N3O2/c1-20(2)10-16(21)18-11-7-8-15-14(9-11)12-5-3-4-6-13(12)17(22)19-15/h3-9H,10H2,1-2H3,(H,18,21)(H,19,22)
|
| Chemical Name |
2-(dimethylamino)-N-(6-oxo-5H-phenanthridin-2-yl)acetamide
|
| Synonyms |
PJ34
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~25 mg/mL (~84.7)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.04 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.04 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3859 mL | 16.9296 mL | 33.8593 mL | |
| 5 mM | 0.6772 mL | 3.3859 mL | 6.7719 mL | |
| 10 mM | 0.3386 mL | 1.6930 mL | 3.3859 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.
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
