| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
PARP7 0.21 nM (IC50) PARP2 0.87 nM (IC50) PARP1 0.94 nM (IC50)
PARP7-IN-16 free base is a selective inhibitor of PARP-1, PARP-2, and PARP-7. PARP enzymes are involved in DNA damage repair, with PARP-1 and PARP-2 playing key roles in the base excision repair (BER) pathway of single-strand DNA breaks. PARP-7 (also known as TIPARP) is a mono(ADP-ribosyl)transferase that has been implicated in cancer cell proliferation and immune evasion. By inhibiting these PARP enzymes, PARP7-IN-16 disrupts DNA repair mechanisms and leads to the accumulation of DNA damage, which can induce cancer cell death, particularly in tumors with defects in homologous recombination repair. |
|---|---|
| ln Vitro |
PARP7-IN-16 free base demonstrates potent in vitro inhibitory activity against PARP-1, PARP-2, and PARP-7, with IC50 values of 0.94 nM, 0.87 nM, and 0.21 nM, respectively. This high potency suggests that the compound effectively inhibits the catalytic activity of these enzymes at low nanomolar concentrations. In cancer cells, PARP7-IN-16 inhibits the repair of DNA damage, leading to the accumulation of DNA strand breaks, activation of DNA damage response pathways, and ultimately induction of cell cycle arrest and apoptosis in PARP-dependent cancer cells.
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| ln Vivo |
PARP7-IN-16 is an orally active PARP inhibitor, making it suitable for in vivo efficacy studies. In mouse models of breast cancer and prostate cancer, treatment with PARP7-IN-16 is expected to inhibit tumor growth, particularly in tumors with BRCA1/2 mutations or other deficiencies in homologous recombination repair. PARP-7 inhibition may also have immunomodulatory effects that could enhance the anti-tumor immune response. The oral bioavailability of the compound facilitates convenient dosing schedules for in vivo studies.
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| Enzyme Assay |
The inhibitory activity of PARP7-IN-16 free base against PARP enzymes can be assessed using a PARP activity assay. Procedure: Recombinant human PARP-1, PARP-2, or PARP-7 enzyme (10 ng/reaction) is incubated with varying concentrations of PARP7-IN-16 (e.g., 0.001, 0.01, 0.1, 1, 10, 100 nM) in 96-well white plates in assay buffer (50 mM Tris-HCl, pH 8.0, 4 mM MgCl2, 0.2 mM DTT, and 50 microg/mL activated DNA). The reaction is initiated by the addition of a biotinylated NAD+ substrate (100 nM) and allowed to proceed for 30 minutes at 37degC. The reaction is stopped by the addition of 0.5 M EDTA. The biotinylated PAR polymers are captured on streptavidin-coated plates and detected with a horseradish peroxidase (HRP)-conjugated anti-PAR antibody. The signal is developed using a chemiluminescent substrate and measured in a luminometer. IC50 values are calculated from dose-response curves.
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| Cell Assay |
PARP inhibition can be assessed in cancer cells by measuring PAR polymer (poly(ADP-ribose)) formation. Procedure: BRCA1/2-deficient cancer cells (e.g., MDA-MB-436 breast cancer cells or C4-2 prostate cancer cells) are seeded in 6-well plates at 5×10^5 cells per well. After 24 hours, cells are treated with varying concentrations of PARP7-IN-16 (e.g., 0.01, 0.1, 1, 10, 100 nM) for 4 hours. To induce DNA damage, cells are then exposed to 1 mM hydrogen peroxide for 10 minutes. Cells are washed with cold PBS and lysed in RIPA buffer containing protease and phosphatase inhibitors. Protein lysates are separated by SDS-PAGE, transferred to PVDF membranes, and immunoblotted with an anti-PAR (poly(ADP-ribose)) antibody. The level of PAR polymer formation is quantified by densitometry. A reduction in PAR polymer levels compared to control indicates PARP inhibition. Cell viability following longer-term treatment (72-96 hours) is measured using CellTiter-Glo assay, and the IC50 value is calculated.
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| Animal Protocol |
In vivo efficacy can be evaluated in a mouse xenograft model of BRCA1/2-deficient breast cancer or prostate cancer. Procedure: 6-8 week old female athymic nude mice are inoculated subcutaneously with 5×10^6 BRCA1-mutant (e.g., MDA-MB-436) or BRCA2-mutant (e.g., Capan-1) cancer cells in 50% Matrigel. When tumors reach an average size of 100-150 mm3, mice are randomized into treatment groups (n=8-10 per group). PARP7-IN-16 is administered orally by gavage at doses of 10, 30, 100 mg/kg once daily for 21-28 days. The positive control group receives olaparib (50 mg/kg, oral), an approved PARP inhibitor. Tumor volumes are measured every 3 days with digital calipers. Body weights are recorded to monitor general toxicity. At study endpoint, tumors are harvested for analysis of PAR polymer levels (by Western blotting), DNA damage markers (gamma-H2AX), and proliferation (Ki-67 immunohistochemistry). Tumor growth inhibition (TGI) is calculated as the percentage reduction in tumor volume compared to the vehicle control group.
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| ADME/Pharmacokinetics |
PARP7-IN-16 is an orally active PARP inhibitor. As such, it is expected to have favorable oral bioavailability (>30%), enabling effective systemic exposure after oral dosing. While specific PK parameters (t1/2, Cmax, AUC) are not provided in the search results, its oral activity in mouse models suggests that the compound is sufficiently stable and permeable to achieve therapeutically relevant concentrations. The molecular weight of 466.50 g/mol and the presence of a fluorine atom (which can improve metabolic stability) are consistent with typical drug-like properties.
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| Toxicity/Toxicokinetics |
Specific toxicity data for PARP7-IN-16 is not available in the search results. As a PARP inhibitor, class-related toxicities include hematological adverse effects (anemia, thrombocytopenia, neutropenia), fatigue, and gastrointestinal effects (nausea, vomiting). PARP inhibitors can also cause myelosuppression due to their effects on hematopoietic stem cells. The selectivity for PARP-1/2/7 may affect the overall toxicity profile. Comprehensive toxicological evaluation would be required for clinical development.
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| References | |
| Additional Infomation |
PARP7-IN-16 free base is a potent and selective inhibitor of PARP-1, PARP-2, and PARP-7, with sub-nanomolar IC50 values for PARP-7 (0.21 nM). PARP inhibitors (PARPis) are a class of targeted cancer therapeutics that exploit the concept of synthetic lethality: cancer cells with BRCA1/2 mutations or other defects in homologous recombination repair are highly sensitive to PARP inhibition because they lack an alternative DNA repair pathway to compensate for PARP loss. PARP-7 (TIPARP) is a mono-PARP that is distinct from the classical PARP-1/2 and has been implicated in cancer cell proliferation and evasion of anti-tumor immunity. Dual inhibition of PARP-1/2 and PARP-7 may provide enhanced anti-tumor activity by combining direct DNA damage induction with immunomodulation. PARP7-IN-16 is being studied for the treatment of breast cancer and prostate cancer, particularly in tumors with homologous recombination repair deficiencies. The free base form is typically the active form of the compound. This compound is for research use only and is not approved for human clinical use. Purity is reported as 99.98%.
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| Molecular Formula |
C25H27FN4O4
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|---|---|
| Molecular Weight |
466.50
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| Exact Mass |
466.202
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| CAS # |
2136325-05-6
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| PubChem CID |
146659481
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
|
| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
|
| Complexity |
804
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC(CC)N1CCN(CC1=O)C(=O)C2=C(C=CC(=C2)CN3C4=CC=CC=C4C(=O)NC3=O)F
|
| InChi Key |
WKXCQZQWHUTWSY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H27FN4O4/c1-3-17(4-2)29-12-11-28(15-22(29)31)24(33)19-13-16(9-10-20(19)26)14-30-21-8-6-5-7-18(21)23(32)27-25(30)34/h5-10,13,17H,3-4,11-12,14-15H2,1-2H3,(H,27,32,34)
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| Chemical Name |
1-[[4-fluoro-3-(3-oxo-4-pentan-3-ylpiperazine-1-carbonyl)phenyl]methyl]quinazoline-2,4-dione
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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 |
| 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 : ~33.33 mg/mL (~71.45 mM; with ultrasonication (<60°C))
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.36 mM) (saturation unknown) in 10% DMSO +40% PEG300 +5% Tween-80 +45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution。
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.36 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 the 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix well. 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: ≥ 2.5 mg/mL (5.36 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 | 2.1436 mL | 10.7181 mL | 21.4362 mL | |
| 5 mM | 0.4287 mL | 2.1436 mL | 4.2872 mL | |
| 10 mM | 0.2144 mL | 1.0718 mL | 2.1436 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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