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| 25mg |
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| Targets |
PARP1-IN-8 targets PARP1 (poly (ADP-ribose) polymerase 1), an enzyme involved in DNA repair processes. PARP1 detects and repairs single-strand DNA breaks by synthesizing poly(ADP-ribose) chains. By inhibiting PARP1, the compound prevents DNA repair and induces synthetic lethality in cancer cells with defective homologous recombination repair. The compound has an IC50 of 97 nM for PARP1. It is BBB-penetrated, making it suitable for central nervous system applications.
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| ln Vitro |
On A549 cells, PARP1-IN-8 (compound 11c) (0–10 μM, 24-48 hours) has a strong and notable anti-proliferative effect [1].
In vitro, PARP1-IN-8 inhibits PARP1 with an IC50 of 97 nM. At concentrations of 0.1, 1, and 10 μM for 24 and 48 hours, the compound shows significantly potent anti-proliferative activity against A549 human lung adenocarcinoma epithelial cells. It does not display any significant cytotoxicity on HFF (human foreskin fibroblasts) cells, indicating a degree of selectivity for cancer cells. |
| ln Vivo |
In vivo, PARP1-IN-8 is expected to show efficacy in animal models of cancer, particularly those with BRCA mutations or other defects in homologous recombination repair. Its ability to penetrate the blood-brain barrier suggests potential applications in brain tumors and neurodegenerative diseases. However, specific in vivo efficacy data and dosing regimens are not extensively detailed in the available literature.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for PARP1-IN-8 typically involve PARP1 activity assays using purified recombinant PARP1 enzyme. The assay is performed in 96-well plates with assay buffer (50 mM Tris-HCl pH 8.0, 10 mM MgCl2, 1 mM DTT). The compound (typically 0.001-100 μM) is incubated with the enzyme, DNA (sonicated calf thymus DNA), and NAD+ (containing biotinylated NAD+) at room temperature for 30-60 minutes. Poly(ADP-ribose) synthesis is detected using streptavidin-HRP and a colorimetric substrate. The IC50 is determined 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[1]. In vitro cellular assays for PARP1-IN-8 use A549 human lung adenocarcinoma epithelial cells and HFF human foreskin fibroblasts. Cells are cultured in DMEM with 10% FBS and treated with various concentrations of the compound (0.1, 1, 10 μM) for 24-48 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. PARP1 inhibition can be confirmed by measuring poly(ADP-ribose) levels in cell lysates using ELISA. DNA damage markers (γH2AX) can be assessed by Western blotting. |
| Animal Protocol |
In vivo animal studies with PARP1-IN-8 would typically use mouse xenograft models of cancer. Immunodeficient mice are implanted subcutaneously with A549 or other cancer cells. When tumors reach approximately 100-200 mm3, mice are treated with the compound at doses of 1-30 mg/kg administered orally or intraperitoneally, daily or every other day for 2-4 weeks. Tumor volume is measured every 2-3 days. At study termination, tumors are harvested for analysis of PARP activity and apoptosis markers.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PARP1-IN-8: The compound is soluble in DMSO at 60 mg/mL (148.57 mM). It has a molecular weight of 403.86 and is BBB-penetrated, indicating good brain penetration. Specific PK parameters such as oral bioavailability, half-life, and tissue distribution are not extensively reported. The compound is expected to be metabolized by hepatic CYP450 enzymes.
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| Toxicity/Toxicokinetics |
The toxicity profile of PARP1-IN-8 shows low cytotoxicity in normal cells, as it does not display any significant cytotoxicity on HFF cells. The compound is for research use only and not for human therapeutic use. Standard toxicity studies would include acute and subchronic toxicity in rodents, with monitoring of body weight, clinical signs, hematology, and clinical chemistry. No specific genotoxicity or cardiotoxicity data are reported.
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| References | |
| Additional Infomation |
PARP1-IN-8 (CAS 836640-15-4, compound 11c) is a potent PARP1 inhibitor with an IC50 of 97 nM. It has a molecular formula of C23H18ClN3O2 and a molecular weight of 403.86. The compound is BBB-penetrated and shows anti-proliferative activity against A549 lung adenocarcinoma cells without significant cytotoxicity on HFF cells. It is used in DNA repair and cancer research and is available for research purposes only.
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| Molecular Formula |
C23H18CLN3O2
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| Molecular Weight |
403.860924243927
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| Exact Mass |
403.108
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| CAS # |
836640-15-4
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| PubChem CID |
3796800
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| Appearance |
White to off-white solid powder
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| LogP |
4.3
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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 |
5
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| Heavy Atom Count |
29
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| Complexity |
632
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CCN1C(=O)C2C(=CC=CC=2)C(C2C=CC=CC=2)=N1)NC1C=C(Cl)C=CC=1
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| InChi Key |
BOYHFRMRSLOWLL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H18ClN3O2/c24-17-9-6-10-18(15-17)25-21(28)13-14-27-23(29)20-12-5-4-11-19(20)22(26-27)16-7-2-1-3-8-16/h1-12,15H,13-14H2,(H,25,28)
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| Chemical Name |
N-(3-chlorophenyl)-3-(1-oxo-4-phenylphthalazin-2-yl)propanamide
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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 : ~62.5 mg/mL (~154.76 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.15 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 | 2.4761 mL | 12.3805 mL | 24.7611 mL | |
| 5 mM | 0.4952 mL | 2.4761 mL | 4.9522 mL | |
| 10 mM | 0.2476 mL | 1.2381 mL | 2.4761 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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