| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
PARP-1 6.3 nM (IC50)
PARP1-IN-29 targets PARP-1, a nuclear enzyme involved in DNA damage repair. PARP-1 detects and repairs single-strand DNA breaks by catalyzing the addition of poly(ADP-ribose) polymers to target proteins. By inhibiting PARP-1 with high potency (IC50 = 6.3 nM), the compound blocks the base excision repair pathway, leading to the accumulation of DNA damage, which is particularly toxic to cancer cells with BRCA1/2 mutations (synthetic lethality). |
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| ln Vitro |
PARP1-IN-29 is a potent PARP-1 inhibitor with an IC50 of 6.3 nM in cell-free biochemical assays. When labeled with [18F], it retains high affinity for PARP-1 and can be used as a PET imaging tracer to visualize PARP-1 expression and activity in tumors. This dual functionality makes it both a therapeutic candidate and a diagnostic imaging probe for oncology research.
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| ln Vivo |
PARP1-IN-29 is an orally active compound suitable for in vivo studies. When labeled with [18F], it can be administered to tumor-bearing mice for PET imaging to detect PARP-1 activity in vivo. As a PARP inhibitor, it is expected to show anti-tumor activity in xenograft models of BRCA-mutant cancers, similar to approved PARP inhibitors such as olaparib and niraparib.
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| Enzyme Assay |
The PARP-1 inhibitory activity of PARP1-IN-29 is measured using a fluorescence-based PARP-1 activity assay. Procedure: Recombinant human PARP-1 enzyme (10 ng) is incubated with varying concentrations of PARP1-IN-29 (0.001-100 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 ug/mL activated DNA). The reaction is initiated by adding biotinylated NAD+ (100 nM) and allowed to proceed for 30 minutes at 37degC. The reaction is stopped with 0.5 M EDTA. The biotinylated PAR polymers are captured on streptavidin-coated plates and detected with HRP-conjugated anti-PAR antibody. Luminescence is measured, and the IC50 is calculated (6.3 nM).
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| Cell Assay |
PARP1-IN-29 can be used in cellular assays to assess PARP inhibition in cancer cell lines. Procedure: BRCA1/2-deficient cancer cells (e.g., MDA-MB-436 breast cancer cells) are seeded in 96-well plates (5x103 cells/well). Cells are treated with serial dilutions of PARP1-IN-29 (0.1-1000 nM) for 72-96 hours. Cell viability is measured using CellTiter-Glo luminescent assay. The IC50 is calculated from dose-response curves. PARP inhibition can also be confirmed by measuring PAR polymer levels via Western blotting. For imaging studies, [18F]-labeled PARP1-IN-29 is incubated with cells, and cellular uptake is measured using a gamma counter.
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| Animal Protocol |
In vivo PET imaging of PARP-1 expression can be performed in a mouse xenograft model. Procedure: Female athymic nude mice are inoculated subcutaneously with 5x10⁶ BRCA1-mutant (e.g., MDA-MB-436) cells in Matrigel. When tumors reach 150-200 mm3, mice are injected intravenously with 100-200 uCi of [18F]-PARP1-IN-29 in saline. Dynamic PET/CT scans are acquired for 60-120 minutes. Region-of-interest (ROI) analysis is performed to quantify radiotracer uptake in tumors and major organs (SUV). Biodistribution is confirmed by harvesting organs at 60 minutes post-injection for gamma counting.
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| ADME/Pharmacokinetics |
PARP1-IN-29 is orally active, indicating favorable oral bioavailability. For PET imaging, the [18F]-labeled compound has a short half-life (110 minutes for 18F), allowing for same-day imaging. The specific PK parameters (t½, Cmax, AUC) for the unlabeled compound are not provided, but its oral activity suggests sufficient metabolic stability and permeability for in vivo applications.
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| Toxicity/Toxicokinetics |
Specific toxicology data for PARP1-IN-29 is not available. As a PARP-1 inhibitor, class-related toxicities include hematological effects (anemia, thrombocytopenia, neutropenia), fatigue, and nausea. The safety profile of PARP1-IN-29 would need to be evaluated in preclinical toxicology studies. Standard laboratory safety precautions for handling radiolabeled compounds should be followed when working with [18F]-labeled material.
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| References | |
| Additional Infomation |
PARP1-IN-29 is a potent PARP-1 inhibitor (IC50 = 6.3 nM) that is orally active and can be labeled with [18F] for PET imaging. This dual-functionality makes it a theranostic agent (therapy + diagnostic imaging) for oncology research. PARP-1 is overexpressed in many cancers, particularly those with defects in homologous recombination repair (e.g., BRCA-mutant breast, ovarian, and pancreatic cancers). PARP1-IN-29 is applicable in the fields of oncology and imaging research for detecting PARP-1 activity in cancer. This product is for research use only and is not an approved drug.
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| Molecular Formula |
C18H16FN3O2
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|---|---|
| Molecular Weight |
325.34
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| Exact Mass |
325.123
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| CAS # |
1567375-93-2
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| PubChem CID |
76324972
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| Appearance |
Solid Powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
456
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CN2C3=C(C=CC=C3N=C2C4=CC=C(C=C4)OCCF)C(=O)N1
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| InChi Key |
DUYPGBKQTGXZRE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H16FN3O2/c19-8-11-24-13-6-4-12(5-7-13)17-21-15-3-1-2-14-16(15)22(17)10-9-20-18(14)23/h1-7H,8-11H2,(H,20,23)
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| Chemical Name |
2-[4-(2-fluoroethoxy)phenyl]-1,3,10-triazatricyclo[6.4.1.04,13]trideca-2,4,6,8(13)-tetraen-9-one
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0737 mL | 15.3685 mL | 30.7371 mL | |
| 5 mM | 0.6147 mL | 3.0737 mL | 6.1474 mL | |
| 10 mM | 0.3074 mL | 1.5369 mL | 3.0737 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.
Products are for research use only; We do not sell to patients
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