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Purity: ≥98%
| Targets |
E7016 targets poly(ADP-ribose) polymerase (PARP) enzymes, specifically PARP1, PARP2, and PARP3. PARP enzymes are involved in DNA repair via the base-excision repair pathway. By inhibiting PARP, E7016 blocks DNA repair, leading to the accumulation of DNA damage in cancer cells. This enhances the sensitivity of tumor cells to DNA-damaging therapies such as radiation and chemotherapy.
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| 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].
In vitro, E7016 inhibits PARP activity, blocking DNA repair. It enhances tumor cell radiosensitivity. The compound shows an in vitro dose enhancement factor (DEF) of 1.4-1.7 across multiple glioblastoma (GBM) cell lines. These activities confirm its role as a radiosensitizer and anticancer agent. E7016 acts as a potential anticancer agent through PARP inhibition. |
| 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].
In vivo, E7016 (40 mg/kg, oral) added a 6-day tumor growth delay in U251 GBM xenografts when combined with radiation/temozolomide (RT/TMZ). It is orally bioavailable and supports repeated-dose gavage in long-term murine models. E7016 enhances tumor cell radiosensitivity in vivo. These findings support its potential as a radiosensitizing and anticancer agent. |
| Enzyme Assay |
In vitro enzyme assays for E7016 measure PARP inhibition using recombinant PARP enzymes. PARP activity is assessed by measuring the incorporation of biotinylated NAD⁺ into histone proteins. Various concentrations of E7016 are added. IC50 values are calculated from dose-response curves. Selectivity for PARP1, PARP2, and PARP3 over other PARP family members is assessed.
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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. Cellular assays for E7016 use cancer cell lines, including glioblastoma (GBM) cell lines. Cells are treated with various concentrations of E7016, with or without radiation or temozolomide. Cell viability is measured using clonogenic assays or MTT assays. DNA repair is assessed by measuring γH2AX foci or comet assays. Radiosensitization is quantified by dose enhancement factor (DEF). |
| 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. In vivo animal studies for E7016 utilize U251 GBM xenograft models in mice. The compound is administered orally at 40 mg/kg. Radiation and/or temozolomide are co-administered. Tumor volume is measured over time. Tumor growth delay is calculated. Efficacy is compared to vehicle and radiation/temozolomide alone. Pharmacodynamic endpoints include PARP inhibition and DNA damage markers. |
| ADME/Pharmacokinetics |
E7016 has molecular weight of 349.4 g/mol and molecular formula C20H19N3O3. It is a solid powder. It is soluble in DMSO, not in water. It is typically stored at 0-4°C for short term or at -20°C for long term. It is orally bioavailable. Pharmacokinetic properties support repeated-dose oral administration.
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| Toxicity/Toxicokinetics |
Preclinical toxicity of E7016 has been evaluated in standard toxicology studies. As a PARP inhibitor, potential adverse effects may include myelosuppression, gastrointestinal effects, and fatigue, which are class effects. The compound's FMO5-mediated Baeyer-Villiger oxidation pathway enables DMPK studies free of CYP3A4/5-related drug-drug interaction confounding. No significant toxicity has been reported at efficacious doses.
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| References |
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| Additional Infomation |
The PARP inhibitor E7016 is a ribonucleotide polymerase (PARP) inhibitor with potential chemosensitizing and/or radiosensitizing activity. E7016 selectively binds to PARP and blocks PARP-mediated single-strand DNA break repair (via the base excision repair pathway). This enhances the accumulation of DNA strand breaks, promotes genomic instability, and ultimately leads to apoptosis. Furthermore, this drug may enhance the cytotoxicity of DNA-damaging drugs and reverse tumor cell resistance to chemotherapy and radiotherapy. PARP catalyzes post-translational ADP-ribosylation modification of nucleoproteins, which signal and recruit other proteins to repair damaged DNA; single-strand DNA breaks activate PARP.
E7016 (GPI 21016) is an orally available PARP1/2/3 inhibitor. It enhances tumor cell radiosensitivity in vitro and in vivo. It has shown efficacy in glioblastoma models in combination with radiation and temozolomide. It is available for research purposes only. |
| 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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