| Targets |
rel-PROTAC PARP1 degrader targets poly(ADP-ribose) polymerase 1 (PARP1) for degradation via the PROTAC (proteolysis-targeting chimera) mechanism. It is based on an MDM2 E3 ligand, which recruits the E3 ubiquitin ligase MDM2 to ubiquitinate PARP1, leading to its proteasomal degradation. PARP1 is a nuclear enzyme involved in DNA repair, and its degradation offers an alternative approach to PARP inhibition for cancer research.
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| ln Vitro |
In vitro studies demonstrate that rel-PROTAC PARP1 degrader is a PARP1 degrader based on an MDM2 E3 ligand. It can significantly induce PARP1 cleavage and programmed cell death. At 10 μM concentration, the compound inhibits MDA-MB-231 breast cancer cells with an IC50 of 6.12 μM at 24 hours. This indicates potent antiproliferative activity against cancer cells through PARP1 degradation.
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| ln Vivo |
In vivo activity of rel-PROTAC PARP1 degrader is inferred from its mechanism as a PARP1 degrader that induces PARP1 cleavage and programmed cell death. By degrading PARP1, the compound may inhibit tumor growth in PARP-dependent cancers. Detailed in vivo efficacy data from animal models are not extensively documented in the available literature. The compound is intended for research use only.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for rel-PROTAC PARP1 degrader is not applicable in the traditional sense, as the compound is a PROTAC degrader rather than a classical enzyme inhibitor. However, cellular degradation assays measure PARP1 protein levels by Western blot after compound treatment. The ability to induce PARP1 cleavage and programmed cell death is assessed. Binding to MDM2 E3 ligase and PARP1 may be assessed using biophysical methods such as surface plasmon resonance or isothermal titration calorimetry.
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| Cell Assay |
In vitro cell-based assays for rel-PROTAC PARP1 degrader are conducted using MDA-MB-231 breast cancer cells. Cells are treated with the compound at various concentrations, and PARP1 protein levels are measured by Western blot to assess degradation. Cell viability and proliferation are assessed using standard assays. At 10 μM, the compound inhibits MDA-MB-231 cells with an IC50 of 6.12 μM at 24 hours. Apoptosis is evaluated by measuring PARP1 cleavage and programmed cell death markers.
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| Animal Protocol |
In vivo animal studies for rel-PROTAC PARP1 degrader would typically be conducted using xenograft mouse models implanted with MDA-MB-231 or other cancer cells. Tumor-bearing mice would be administered the compound via appropriate routes, and tumor growth inhibition would be monitored. PARP1 degradation in tumor tissues would be confirmed by Western blot. Pharmacokinetic parameters would be determined from plasma samples. However, detailed protocols and efficacy data are not available from the search results.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of rel-PROTAC PARP1 degrader are not extensively documented in the available literature. As a PROTAC molecule, it has a larger molecular weight compared to traditional small-molecule inhibitors, which may affect oral bioavailability and tissue distribution. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability are not available from the search results. The compound is intended for research use only.
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| Toxicity/Toxicokinetics |
Toxicity information for rel-PROTAC PARP1 degrader is limited. Standard safety precautions for handling research chemicals should be followed. The compound is designated for research use only and is not for human therapeutic applications. As a PROTAC degrader, it may have off-target effects and potential toxicity that should be evaluated in appropriate studies. No detailed toxicity data are available from the search results.
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| References | |
| Additional Infomation |
rel-PROTAC PARP1 degrader is a PARP1 degrader based on an MDM2 E3 ligand that induces PARP1 cleavage and programmed cell death. At 10 μM, it inhibits MDA-MB-231 cells with an IC50 of 6.12 μM at 24 hours. It is the relative configuration of ROTAC PARP1 degrader . It is intended for research use only.
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| Molecular Formula |
C58H63CL2N11O10
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|---|---|
| Molecular Weight |
1145.09
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| Appearance |
Solid powder
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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) |
Typically soluble in DMSO (e.g. 10 mM)
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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 | 0.8733 mL | 4.3665 mL | 8.7329 mL | |
| 5 mM | 0.1747 mL | 0.8733 mL | 1.7466 mL | |
| 10 mM | 0.0873 mL | 0.4366 mL | 0.8733 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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