| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
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| Targets |
PARP ( IC50 = 110 nM ); PARP-2 ( IC50 = 86 nM ); PARP-1 ( IC50 = 110 nM )
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| 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].
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| 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].
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| 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.
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| 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.
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| 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.
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| References |
[1]. Iwashita A, et al. A novel and potent poly(ADP-ribose) polymerase-1 inhibitor, FR247304 (5-chloro-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazolinone), attenuates neuronal damage in in vitro and in vivo models of cerebral ischemia. J Ph
[2]. Haddad M, et al. Anti-inflammatory effects of PJ34, a poly(ADP-ribose) polymerase inhibitor, in transient focal cerebral ischemia in mice. Br J Pharmacol. 2006 Sep;149(1):23-30 |
| Molecular Formula |
C17H17N3O2
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|---|---|
| Molecular Weight |
295.3358
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| Exact Mass |
295.13
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| CAS # |
344458-19-1
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| Related CAS # |
PJ34 hydrochloride;344458-15-7
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| Appearance |
Powder
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| SMILES |
CN(C)CC(=O)NC1=CC2=C(C=C1)NC(=O)C3=CC=CC=C32
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| InChi Key |
UYJZZVDLGDDTCL-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
2-(dimethylamino)-N-(6-oxo-5H-phenanthridin-2-yl)acetamide
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| Synonyms |
PJ34
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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: ~25 mg/mL (~84.7)
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| 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.
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