| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
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| 1g |
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| Other Sizes |
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| Targets |
PARP1; MDM2 E3 ligase
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|---|---|
| ln Vitro |
Poly (ADP-ribose) polymerase-1 (PARP1) is a major member of the PARP superfamily that is involved in DNA damage signalling and other important cellular processes. Here researchers report the development of a small molecule targeting PARP1 based on the PROTAC strategy. In the MDA-MB-231 cell line, the representative compound 3 can induce significant PARP1 cleavage and programmed cell death [1].
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| Cell Assay |
Western Blotting [1]
Cells were lysed for 20 min on ice using RIPA buffer with added protease inhibitor cocktail and PMSF. The lysate was spun at 14,000 g for 15 min at 4 °C. Supernatant was collected and protein quantified using BCA Protein Assay. 40μg of protein were loaded into 8% SDS-PAGE gel. Proteins were transferred onto a PVDF methanol activated membrane using a wet transfer method. Membranes were blocked in 5% non-fat milk diluted in 1xTBST for 1 hour at room temperature while gently rocking. Primary antibodies (listed below) were incubated in 5% BSA in 1x TBST and gently rocked overnight at 4°C. HRP-conjugated secondary antibodies diluted at 1: 3,000 were incubated in 1xTBST and rocked for 1 hour at room temperature. ECL chemiluminescence kit was used to detect protein expression. Western blot images were captured by Tanon 5200 chemiluminescent imaging system. Quantification of band intensities has been performed using Tanon Gis software. Cell Viability Assay[1] Cell viability was evaluated using the Cell Counting Kit-8 (CCK-8) assay. 5x10~3 cells/well were seeded in a 96-well plate. After growing for 24 or 48 hours, cells were treated with indicated reagents. Each group had triplicate wells. After incubation for the indicated hours, 10 μL CCK-8 reagent was added to each well. After incubation for 2-4 hour, the Optical density (OD) values at 490 nm were measured with a microplate reader. Data was analyzed using GraphPad Prism 7.0. Error bars represent ± SD for three independent experiments. |
| References | |
| Additional Infomation |
The nuclear enzymes called poly(ADP-ribose)polymerases (PARPs) are known to catalyze the process of PARylation, which plays a vital role in various cellular functions. They have become important targets for the discovery of novel antitumor drugs since their inhibition can induce significant lethality in tumor cells. Therefore, researchers all over the world have been focusing on developing novel and potent PARP inhibitors for cancer therapy. Studies have shown that PARP inhibitors and other antitumor agents, such as EZH2 and EGFR inhibitors, play a synergistic role in cancer cells. The combined inhibition of PARP and the targets with synergistic effects may provide a rational strategy to improve the effectiveness of current anticancer regimens. In this Perspective, we sum up the recent advance of PARP-targeted agents, including single-target inhibitors/degraders and dual-target inhibitors/degraders, discuss the fundamental theory of developing these dual-target agents, and give insight into the corresponding structure-activity relationships of these agents. J Med Chem. 2022 Dec 22;65(24):16099-16127.
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| Molecular Weight |
1145.09
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|---|---|
| Exact Mass |
1143.413
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| CAS # |
2369022-68-2
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| PubChem CID |
138454769
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.661
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| LogP |
3.88
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
26
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| Heavy Atom Count |
81
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| Complexity |
2030
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| Defined Atom Stereocenter Count |
2
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| SMILES |
N1=C2C(C=CC=C2C(N)=O)=CN1C1=CC=C(C2=CN(CCOCCOCCOCCOCCNC(=O)CN3CCN(C(N4C(C5=CC=C(OC)C=C5OC(C)C)=N[C@H](C5=CC=C(Cl)C=C5)[C@@H]4C4=CC=C(Cl)C=C4)=O)CC3=O)N=N2)C=C1
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| InChi Key |
RQWKTYKJNCZUJW-OMUYKDLESA-N
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| InChi Code |
InChI=1S/C58H63Cl2N11O10/c1-38(2)81-50-33-46(76-3)19-20-47(50)57-63-54(40-7-13-43(59)14-8-40)55(41-9-15-44(60)16-10-41)71(57)58(75)68-23-22-67(52(73)37-68)36-51(72)62-21-25-77-27-29-79-31-32-80-30-28-78-26-24-69-35-49(64-66-69)39-11-17-45(18-12-39)70-34-42-5-4-6-48(56(61)74)53(42)65-70/h4-20,33-35,38,54-55H,21-32,36-37H2,1-3H3,(H2,61,74)(H,62,72)/t54-,55+/m1/s1
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| Chemical Name |
2-[4-[1-[2-[2-[2-[2-[2-[[2-[4-[(4R,5S)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]-2-oxopiperazin-1-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]phenyl]indazole-7-carboxamide
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| Synonyms |
PROTAC PARP1 degrader; 2369022-68-2; rel-PROTAC PARP1 degrader; PARP1-targeting PROTAC 3; CHEMBL5284804;
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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 | 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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