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| Targets |
PARP-1-IN-2 targets poly(ADP-ribose) polymerase 1 (PARP-1), an enzyme crucial for DNA repair and maintaining genomic stability. PARP-1 detects and repairs single-strand DNA breaks by catalyzing the addition of ADP-ribose polymers to target proteins. Inhibition of PARP-1 leads to the accumulation of DNA damage and cell death, particularly in cancer cells with defective homologous recombination repair (e.g., BRCA-mutant cells). PARP-1-IN-2 is a potent inhibitor with an IC₅₀ of 149 nM.
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| ln Vitro |
On A549 cells, PARP-1-IN-2 (compound 11g) (0–10 μM, 24-48 hours) exhibits strong and notable anti-proliferative activity [1]. In a 24-hour period, PARP-1-IN-2 (0-10 μM) decreases the expression of phosphorylated AKT and caspase-3 precursor while increasing the expression of cleaved PARP-1, caspase-9 protein, and caspase-3[1].
PARP-1-IN-2 shows significant anti-proliferative activity against the human lung adenocarcinoma epithelial cell line A549 in cellular assays. It induces apoptosis in A549 cells. The compound inhibits PARP1 enzymatic activity with an IC₅₀ of 149 nM. It also crosses the blood-brain barrier, suggesting potential for treating brain tumors. These activities make it a valuable tool for studying PARP1 biology and cancer therapy. |
| ln Vivo |
In vivo activity data for PARP-1-IN-2 are not extensively documented in the literature. Based on its potent in vitro PARP1 inhibition and anti-proliferative activity against cancer cells, it is anticipated to have potential in vivo antitumor efficacy, particularly against tumors with defective DNA repair. Its ability to cross the blood-brain barrier suggests potential for treating brain tumors. Specific animal studies are not extensively documented.
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| Enzyme Assay |
The non-cellular enzyme/receptor binding assay for PARP-1-IN-2 typically involves measuring PARP1 enzymatic activity using a colorimetric or radiometric assay. Recombinant PARP1 enzyme is incubated with DNA (to activate the enzyme), NAD⁺ (the substrate), and varying concentrations of PARP-1-IN-2. The incorporation of ADP-ribose into acceptor proteins or the consumption of NAD⁺ is measured. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Cell proliferation assay
Cell Types: A549, HFF cells [1] Tested Concentrations: 0, 0.1, 1, 10 μM Incubation Duration: 24, 48 hrs (hours) Experimental Results: demonstrated Dramatically effective anti-proliferative activity against A549 cells and did not show any significant Significant anti-proliferative activity. Cytotoxicity to HFF cells. Western Blot Analysis Cell Types: A549 cells [1] Tested Concentrations: 0, 0.1, 1, 10 μM Incubation Duration: 24 h Experimental Results: The expression of pro-caspase-3 and phosphorylated AKT diminished, and the expression of caspase-3 and caspase increased Dramatically - 9 protein and enhanced the expression of cleaved PARP-1. In vitro cellular assays for PARP-1-IN-2 typically use human lung adenocarcinoma A549 cells. Cells are treated with various concentrations of the compound for 24-72 hours. Cell proliferation is assessed using MTT, CCK-8, or colony formation assays. Apoptosis is detected by Annexin V/PI staining, caspase activity assays, and PARP cleavage by Western blotting. DNA damage can be assessed by γ-H2AX staining. The IC₅₀ for anti-proliferative activity is determined. |
| Animal Protocol |
In vivo animal studies for PARP-1-IN-2 are not extensively documented. Based on its PARP1 inhibitory mechanism and ability to cross the blood-brain barrier, typical study designs would involve xenograft mouse models of lung cancer or brain tumors. PARP-1-IN-2 would be administered orally or intraperitoneally. Tumor growth inhibition, body weight changes, and survival rates would be monitored. Tumor tissues would be analyzed for PARP1 inhibition, apoptosis markers, and DNA damage.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PARP-1-IN-2 are not extensively characterized in the literature. The compound is described as being able to penetrate the blood-brain barrier, indicating favorable CNS penetration. As a small molecule with molecular weight 424.28, it is expected to have reasonable oral bioavailability. Specific PK parameters such as half-life, Cmax, and protein binding are not well documented. Further pharmacokinetic studies would be needed.
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| Toxicity/Toxicokinetics |
Toxicological data for PARP-1-IN-2 are limited. As a research-grade compound, comprehensive toxicology studies are not available. PARP inhibitors are generally well-tolerated, with common adverse effects including fatigue, nausea, and hematological toxicities. However, specific toxicity data for this compound are not documented. Standard laboratory safety precautions should be observed when handling this compound.
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| References | |
| Additional Infomation |
PARP-1-IN-2 is a research-grade compound intended for laboratory use only. It is not approved for clinical use as a therapeutic agent. Its primary applications include studying PARP1 biology and DNA repair mechanisms, investigating the therapeutic potential of PARP inhibitors in cancer, particularly in tumors with defective DNA repair, and exploring PARP1 inhibition in the context of brain tumors due to its ability to cross the blood-brain barrier.
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| Molecular Formula |
C22H15CL2N3O2
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|---|---|
| Molecular Weight |
424.2794
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| Exact Mass |
423.054
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| CAS # |
684234-55-7
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| PubChem CID |
1987353
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| Appearance |
White to off-white solid powder
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| LogP |
5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
648
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])C1C2=C([H])C([H])=C([H])C([H])=C2C(N(C([H])([H])C(N([H])C2C([H])=C([H])C([H])=C(C=2[H])Cl)=O)N=1)=O
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| InChi Key |
ASIIOGZHCMSESG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H15Cl2N3O2/c23-15-10-8-14(9-11-15)21-18-6-1-2-7-19(18)22(29)27(26-21)13-20(28)25-17-5-3-4-16(24)12-17/h1-12H,13H2,(H,25,28)
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| Chemical Name |
N-(3-chlorophenyl)-2-[4-(4-chlorophenyl)-1-oxophthalazin-2-yl]acetamide
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~83.33 mg/mL (~196.40 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.90 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.90 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3569 mL | 11.7847 mL | 23.5693 mL | |
| 5 mM | 0.4714 mL | 2.3569 mL | 4.7139 mL | |
| 10 mM | 0.2357 mL | 1.1785 mL | 2.3569 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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