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Purity: ≥98%
E7016, formerly known as GPI21016, is an inhibitor of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) with potential chemo- and/or radiosensitizing activity. PARP inhibitor E7016 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks and promotes genomic instability and eventually leads to apoptosis. In addition, this agent may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapy and radiation therapy. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks. References: Lai WG, Farah N, Moniz GA, Wong YN. A Baeyer-Villiger oxidation specifically catalyzed by human flavin-containing monooxygenase 5. Drug Metab Dispos. 2011 Jan;39(1):61-70. Epub 2010 Oct 14. PubMed PMID: 20947616.
| ln Vitro |
By preventing DNA repair, E7016 can increase the radiosensitivity of tumor cells [1]. Increasing the number of cells undergoing mitotic catastrophe instead of increasing the number of cells undergoing apoptosis is how E7016 (3 μM)-mediated radiosensitization is accomplished [1]. By imitating NAD+, E7016 inhibits PARP[2].
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| ln Vivo |
In mice xenograft trials, E7016 possesses anti-tumor efficaciousness [1]. When E7016 (40 mg/kg) was given orally to mice that were carrying U251 xenografts, the combination of radiation and temozolomide was more successful [1]. In comparison to the in vivo combination of temozolomide and radiation, mice treated with E7016/radiotherapy/temozolomide showed a six-day growth delay [1].
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| Cell Assay |
Apoptosis analysis [1]
Cell Types: U251 human glioblastoma cell line Tested Concentrations: 3 μM Incubation Duration: 6 hrs (hours) before irradiation, 24 hrs (hours) and 72 hrs (hours) after irradiation Staining Experimental Results: The number of cells undergoing mitotic catastrophe was obvious in E7016 Increased - treated irradiated cells compared to cells exposed to radiation only 24 hrs (hours) after irradiation. |
| Animal Protocol |
Animal/Disease Models: Four to six week old female nude mice [3]
Doses: 40 mg/kg Route of Administration: po (oral gavage) Experimental Results: E7016 enhanced radiation/temozolomide (3 mg/kg orally)-induced delayed tumor growth in U251 xenografts. |
| References |
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| Additional Infomation |
PARP Inhibitor E7016 is an inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential chemo- and/or radiosensitizing activity. PARP inhibitor E7016 selectively binds to PARP and prevents PARP mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks and promotes genomic instability and eventually leads to apoptosis. In addition, this agent may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapy and radiation therapy. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks.
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| Molecular Formula |
C20H19N3O3
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|---|---|
| Molecular Weight |
349.383
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| Exact Mass |
349.143
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| CAS # |
902128-92-1
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| Related CAS # |
1005412-29-2 (deleted);902128-92-1;E7016 HCl;
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| PubChem CID |
11660296
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| Appearance |
White to off-white solid powder
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| LogP |
3.002
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
587
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
HAVFFEMDLROBGI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19N3O3/c24-13-6-8-23(9-7-13)11-12-4-5-16-15(10-12)19-18-14(20(25)22-21-19)2-1-3-17(18)26-16/h1-5,10,13,24H,6-9,11H2,(H,22,25)
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| Chemical Name |
10-((4-Hydroxypiperidin-1-yl)methyl)chromeno[4,3,2-de]phthalazin-3(2H)-one
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| Synonyms |
E7016 E-7016 E 7016 GPI21016 GPI 21016 GPI-21016.
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~25 mg/mL (~71.56 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.58 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 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 1.25 mg/mL (3.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8622 mL | 14.3111 mL | 28.6221 mL | |
| 5 mM | 0.5724 mL | 2.8622 mL | 5.7244 mL | |
| 10 mM | 0.2862 mL | 1.4311 mL | 2.8622 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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