E7016
(Synonyms: GPI 21016) 目录号 : GC64209
E7016 (GPI 21016) 是一种口服有效的 PARP 抑制剂。E7016 可以通过抑制 DNA 修复来增强肿瘤细胞在体内外的放射敏感性。E7016 用作一种潜在的抗肿瘤剂。
Cas No.:902128-92-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
E7016 (GPI 21016) is an orally available PARP inhibitor. E7016 can enhance tumor cell radiosensitivity in vitro and in vivo through the inhibition of DNA repair. E7016 acts as a potential anticancer agent[1][2].
E7016 can enhance tumor cell radiosensitivity through the inhibition of DNA repair[1].E7016 (3 μM)-mediated radiosensitization occurs through an increase in the number of cells undergoing mitotic catastrophe and not an increase in the number of cells undergoing apoptosis[1].E7016 inhibits PARP by mimicking NAD+[2].
E7016 has antitumor efficacy in murine xenograft studies[1].Administration of E7016 (40 mg/kg; oral gavage) to mice bearing U251 xenografts enhances the effectiveness of the Temozolomide/radiation combination[1]. Mice treated with E7016/irradiation/Temozolomide have an additional growth delay of six days compared with the combination of Temozolomide and irradiation in vivo[1].
[1]. Andrea L Russo, et al. In vitro and in vivo radiosensitization of glioblastoma cells by the poly (ADP-ribose) polymerase inhibitor E7016. Clin Cancer Res. 2009 Jan 15;15(2):607-12.
[2]. W George Lai, et al. A Baeyer-Villiger oxidation specifically catalyzed by human flavin-containing monooxygenase 5. Drug Metab Dispos. 2011 Jan;39(1):61-70.
| Cas No. | 902128-92-1 | SDF | Download SDF |
| 别名 | GPI 21016 | ||
| 分子式 | C20H19N3O3 | 分子量 | 349.38 |
| 溶解度 | DMSO : 25 mg/mL (71.56 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
In vitro and in vivo radiosensitization of glioblastoma cells by the poly (ADP-ribose) polymerase inhibitor E7016
Clin Cancer Res 2009 Jan 15;15(2):607-12.PMID:19147766DOI:10.1158/1078-0432.CCR-08-2079.
Purpose: Poly (ADP-ribose) polymerase (PARP) inhibitors are undergoing clinical evaluation for cancer therapy. Because PARP inhibition has been shown to enhance tumor cell sensitivity to radiation, we investigated the in vitro and in vivo effects of the novel PARP inhibitor E7016. Experimental design: The effect of E7016 on the in vitro radiosensitivity of tumor cell lines was evaluated using clonogenic survival. DNA damage and repair were measured using gammaH2AX foci and neutral comet assay. Mitotic catastrophe was determined by immunostaining. Tumor growth delay was evaluated in mice for the effect of E7016 on in vivo (U251) tumor radiosensitivity. Results: Cell lines exposed to E7016 preirradiation yielded an increase in radiosensitivity with dose enhancement factors at a surviving fraction of 0.1 from 1.4 to 1.7. To assess DNA double-strand breaks repair, gammaH2AX measured at 24 hours postirradiation had significantly more foci per cell in the E7016/irradiation group versus irradiation alone. Neutral comet assay further suggested unrepaired double-strand breaks with significantly greater DNA damage at 6 hours postirradiation in the combination group versus irradiation alone. Mitotic catastrophe staining revealed a significantly greater number of cells staining positive at 24 hours postirradiation in the combination group. In vivo, mice treated with E7016/irradiation/temozolomide had an additional growth delay of six days compared with the combination of temozolomide and irradiation. Conclusions: These results indicate that E7016 can enhance tumor cell radiosensitivity in vitro and in vivo through the inhibition of DNA repair. Moreover, enhanced growth delay with the addition of E7016 to temozolomide and radiotherapy in a glioma mouse model suggests a potential role for this drug in the treatment of glioblastoma multiforme.
A Baeyer-Villiger oxidation specifically catalyzed by human flavin-containing monooxygenase 5
Drug Metab Dispos 2011 Jan;39(1):61-70.PMID:20947616DOI:10.1124/dmd.110.035360.
10-((4-Hydroxypiperidin-1-yl)methyl)chromeno[4,3,2-de]phthalazin-3(2H)-one (E7016), an inhibitor of poly(ADP-ribose) polymerase, is being developed for anticancer therapy. One of the major metabolites identified in preclinical animal studies was the product of an apparent oxidation and ring opening of the 4-hydroxypiperidine. In vitro, this oxidized metabolite could not be generated by incubating E7016 with animal or human liver microsomes. Further studies revealed the formation of this unique metabolite in hepatocytes. In a NAD(P)(+)-dependent manner, this metabolite was also generated by liver S9 fractions and recombinant human flavin-containing monooxygenase (FMO) 5 that was fortified with liver cytosol fractions. In animal and human liver S9, this metabolic pathway could be inhibited by 4-methylpyrazole, bis-p-nitrophenylphosphate (BNPP), or a brief heat treatment at 50°C. Based on these results, the overall metabolic pathway was believed to involve a two-step oxidation process: dehydrogenation of the secondary alcohol in liver cytosol followed by an FMO5-mediated Baeyer-Villiger oxidation in liver microsomes. The two oxidation steps were coupled via regeneration of NAD(P)(+) and NAD(P)H. To further confirm this mechanism, the proposed ketone intermediate was independently synthesized. In an NAD(P)H-dependent manner, the synthetic ketone intermediate was metabolized to the same ring-opened metabolite in animal and human liver microsomes. This metabolic reaction was also inhibited by BNPP or a brief heat treatment at 50°C. Methimazole, the substrate/inhibitor of FMO1 and FMO3, did not inhibit this reaction. The specificity of FMO5 toward catalyzing this Baeyer-Villiger oxidation was further demonstrated by incubating the synthetic ketone intermediate in recombinant enzymes.
Anthropometric Measurements and Lifestyle Characteristics of Individuals with Non-alcoholic Fatty Liver Disease
Cureus 2020 Feb 17;12(2):E7016.PMID:32211252DOI:10.7759/cureus.7016.
Background Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder caused by the deposition of lipids and fats in the hepatocytes, in individuals who consume little or no alcohol, which eventually progresses to cirrhosis and carcinoma. Apart from the known risk factors like obesity, metabolic syndrome (MS), and lack of physical activity (PA), diet also plays a major role in the development of NAFLD. A high body mass index (BMI) and waist circumference (WC) have positive associations with NAFLD. The aim of this study was to find the prevalence of risk factors of hepatic steatosis in NAFLD population and to raise public awareness about the condition. Method We conducted a cross-sectional study from October to December 2019 with a sample size of 98 subjects determined by using a confidence interval (CI) of 99.9%. Patients presenting to Essa Laboratory, Karachi for abdominal ultrasound (US) were scanned for fatty changes in the liver, after obtaining consent, and were then assessed for risk factors by administering a 20-item questionnaire along with registering their BMI and WC measurement. The collected data was analyzed using the Statistical Package for Social Sciences (SPSS), version 22 (IBM, Armonk, NY). The independent sample t-test was applied for the exploration of variables and a p-value <0.05 was considered significant. Result Our study included 96 participants, of which 49 (51%) were male and 47 (49%) female. Mean BMI in females was slightly greater (30.58) than in males (27.98), whereas WC (in inches) was almost equal in males (40.796) and females (40.383). Among the people that had any comorbidities (n = 60, 62.5%), hypertension (HTN) was the most common one (n = 37, 38.5%) followed by diabetes mellitus (DM) type 2 (n = 26, 27.1%). A significant majority (n = 63, 65.5%) never consumed any fruits or vegetables in their meal nor did they perform any sort of physical exercise (n = 46, 47.9%). Conclusion Obesity (high BMI), lack of PA, lower consumption of fruits and vegetables along with a carbohydrate- and fat-rich diet play a vital role in the development of hepatic steatosis. Moreover, HTN and DM, as components of MS, exhibit a significant association with NAFLD. Screening and counseling sessions should be considered for individuals with these anthropometric measurements and lifestyle characteristics.
A case of adult patent ductus arteriosus-associated infective endarteritis who was successfully treated with only antibiotics
Clin Case Rep 2023 Mar 14;11(3):E7016.PMID:36937627DOI:10.1002/ccr3.7016.
Patent ductus arteriosus-associated infective endarteritis (PDA-IE) is an extremely rare complication of PDA in recent years. In this report, we describe a case of PDA-IE complicated by septic pulmonary embolism who was successfully treated with only antibiotics.
One-class land-cover classification using MaxEnt: the effect of modelling parameterization on classification accuracy
PeerJ 2019 May 27;7:E7016.PMID:31179194DOI:10.7717/peerj.7016.
Multiple-class land-cover classification approaches can be inefficient when the main goal is to classify only one or a few classes. Under this scenario one-class classification algorithms could be a more efficient alternative. Currently there are several algorithms that can fulfil this task, with MaxEnt being one of the most promising. However, there is scarce information regarding parametrization for performing land-cover classification using MaxEnt. In this study we aimed to understand how MaxEnt parameterization affects the classification accuracy of four different land-covers (i.e., built-up, irrigated grass, evergreen trees and deciduous trees) in the city of Santiago de Chile. We also evaluated if MaxEnt manual parameterization outperforms classification results obtained when using MaxEnt default parameters setting. To accomplish our objectives, we generated a set of 25,344 classification maps (i.e., 6,336 for each assessed land-cover), which are based on all the potential combination of 12 different classes of features restrictions, four regularization multipliers, four different sample sizes, three training/testing proportions, and 11 thresholds for generating the binary maps. Our results showed that with a good parameterization, MaxEnt can effectively classify different land covers with kappa values ranging from 0.68 for deciduous trees to 0.89 for irrigated grass. However, the accuracy of classification results is highly influenced by the type of land-cover being classified. Simpler models produced good classification outcomes for homogenous land-covers, but not for heterogeneous covers, where complex models provided better outcomes. In general, manual parameterization improves the accuracy of classification results, but this improvement will depend on the threshold used to generate the binary map. In fact, threshold selection showed to be the most relevant factor impacting the accuracy of the four land-cover classification. The number of sampling points for training the model also has a positive effect on classification results. However, this effect followed a logarithmic distribution, showing an improvement of kappa values when increasing the sampling from 40 to 60 points, but showing only a marginal effect if more than 60 sampling points are used. In light of these results, we suggest testing different parametrization and thresholds until satisfactory kappa or other accuracy metrics values are achieved. Our results highlight the huge potential that MaxEnt has a as a tool for one-class classification, but a good understanding of the software settings and model parameterization is needed to obtain reliable results.