PJ34 HCl, the hydrochloride of PJ34, is a novel, potent and selective inhibitor of poly(ADP-ribose) polymerase (PARP) with potential anticancer and neuro-protective activities. In a cell-free assay, it inhibits PARP with an EC50 value of 20 nM. In a variety of tumor types, PJ34 has neuro-protective properties and can strengthen the effects of chemotherapy.
Physicochemical Properties
| Molecular Formula | C17H17N3O2.HCL | |
| Molecular Weight | 331.8 | |
| Exact Mass | 331.11 | |
| Elemental Analysis | C, 61.54; H, 5.47; Cl, 10.68; N, 12.66; O, 9.64 | |
| CAS # | 344458-15-7 | |
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| PubChem CID | 16760621 | |
| Appearance | Light yellow to yellow solid powder | |
| Boiling Point | 539.1ºC at 760 mmHg | |
| Flash Point | 279.9ºC | |
| LogP | 3.114 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 3 | |
| Rotatable Bond Count | 3 | |
| Heavy Atom Count | 23 | |
| Complexity | 438 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | Cl[H].O=C1C2=C([H])C([H])=C([H])C([H])=C2C2C([H])=C(C([H])=C([H])C=2N1[H])N([H])C(C([H])([H])N(C([H])([H])[H])C([H])([H])[H])=O |
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| InChi Key | RURAZZMDMNRXMI-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C17H17N3O2.ClH/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);1H | |
| Chemical Name | 2-(dimethylamino)-N-(6-oxo-5H-phenanthridin-2-yl)acetamide;hydrochloride | |
| Synonyms | PJ-34 hydrochloride; PJ-34 HCl; PJ-34; PJ34; PJ 34 | |
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | PARP ( IC50 = 110 nM ); PARP-2 ( IC50 = 86 nM ); PARP-1 ( IC50 = 110 nM ) | |
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| ln Vivo |
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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. The reaction is stopped by adding 200 μL of ice-cold 20% trichloroacetic acid (TCA) and incubating at 4°C for 10 minutes.The reaction mixture is then incubated at room temperature (23°C) for 15 minutes. Following three rounds of washing with 70% ethanol and 10% TCA solution, the precipitate is moved to a GF/B filter. Liquid scintillation counting determines the radioactivity after the filter has dried. | |
| 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. | |
| Animal Protocol |
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| References |
[1]. 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 Pharmacol Exp Ther. 2004 Aug;310(2):425-36. [2]. 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. [3]. NAD+ loss, a new player in AhR biology: prevention of thymus atrophy and hepatosteatosis by NAD+ repletion. Sci Rep. 2017 May 23;7(1):2268. |
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| Additional Infomation | PJ34 hydrochloride is a hydrochloride salt prepared from equimolar amounts of PJ34 and hydrochloric acid. It has a role as an angiogenesis inhibitor, an anti-inflammatory agent, an antiatherosclerotic agent, an antineoplastic agent, an apoptosis inducer, a cardioprotective agent, an EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor and a neuroprotective agent. It contains a PJ34(1+). |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (3.01 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (3.01 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 10.0 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. Solubility in Formulation 3: ≥ 1 mg/mL (3.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% propylene glycol: 14 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0139 mL | 15.0693 mL | 30.1386 mL | |
| 5 mM | 0.6028 mL | 3.0139 mL | 6.0277 mL | |
| 10 mM | 0.3014 mL | 1.5069 mL | 3.0139 mL |