| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
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iRucaparib-AP6 is a novel and potent PARP1 degrader based on PROTAC (Proteolysis-targeting chimera) technology. It is composed of Rucaparib as the warhead to bind PARP1 and pomalidomide to recruit the E3 ligase. iRucaparib-AP6 blocks the enzymatic activity of PARP1 in vitro, and PARP1-mediated poly-ADP-ribosylation signaling in intact cells. This strategy mimics PARP1 genetic depletion, which enables the pharmacological decoupling of PARP1 inhibition from PARP1 trapping. Finally, by depleting PARP1, iRucaparib-AP6 protects muscle cells and primary cardiomyocytes from DNA-damage-induced energy crisis and cell death.
| ln Vitro |
In a time-dependent manner, iRucaparib-AP6 (0-10 μM; 24 hours) lowers PARP-1 levels, with a half-maximal degradation concentration (DC50 = 92%) of 82 nM (Dmax) [1].
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|---|---|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: Primary rat neonatal cardiomyocytes ( Tested Concentrations: 0.001 μM; 0 -20 μM; 24 hrs (hours)) induces PARP1 degradation at low concentrations[1]. 0.01μM; 0.1μM; 1μM; 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: PARP-1 levels were diminished in primary rat neonatal cardiomyocytes. Western Blot Analysis [1] Cell Types: Primary rat neonatal cardiomyocytes Tested Concentrations: 0.05 μM; 0.1 μM; 0.2 μM; 0.5 μM; 1 μM; 2 μM; 5 μM; 10 μM; 20 μM Incubation Duration: 24 hrs (hours) Experimental Results: Concentrations as low as Strong degradation of PARP1 is induced at 50 nM. |
| References |
| Molecular Formula |
C46H55FN6O11
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|---|---|
| Molecular Weight |
886.9609
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| Exact Mass |
886.391
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| CAS # |
2410557-00-3
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| PubChem CID |
138857977
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
26
|
| Heavy Atom Count |
64
|
| Complexity |
1540
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=C([H])C2C(N([H])C([H])([H])C([H])([H])C3=C(C4C([H])=C([H])C(C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])N([H])C5=C([H])C([H])=C([H])C6C(N(C(C=65)=O)C5([H])C(N([H])C(C([H])([H])C5([H])[H])=O)=O)=O)=C([H])C=4[H])N([H])C(=C1[H])C3=2)=O
|
| InChi Key |
YHMDCINUVWULST-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C46H55FN6O11/c1-52(29-30-5-7-31(8-6-30)42-33-11-12-49-43(55)35-27-32(47)28-37(50-42)40(33)35)14-16-60-18-20-62-22-24-64-26-25-63-23-21-61-19-17-59-15-13-48-36-4-2-3-34-41(36)46(58)53(45(34)57)38-9-10-39(54)51-44(38)56/h2-8,27-28,38,48,50H,9-26,29H2,1H3,(H,49,55)(H,51,54,56)
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| Chemical Name |
2-(2,6-dioxopiperidin-3-yl)-4-[2-[2-[2-[2-[2-[2-[2-[[4-(6-fluoro-9-oxo-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-2-yl)phenyl]methyl-methylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]isoindole-1,3-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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~50 mg/mL (~56.37 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.82 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.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1274 mL | 5.6372 mL | 11.2745 mL | |
| 5 mM | 0.2255 mL | 1.1274 mL | 2.2549 mL | |
| 10 mM | 0.1127 mL | 0.5637 mL | 1.1274 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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