E 2012
(Synonyms: (E)-1-[(1S)-1-(4-氟苯基)乙基]-3-[3-甲氧基-4-(4-甲基-1H-咪唑-1-YL)亚苄基]哌啶-2-酮) 目录号 : GC35921
A γ-secretase modulator
Cas No.:870843-42-8
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
E2012 is a modulator of γ-secretase.1 It selectively inhibits APP intracellular signaling domain (AICD) cleavage to amyloid-β (Aβ) over Notch cleavage to its signaling effector Notch intracellular domain (NICD), processes both mediated by γ-secretase, when used at a concentration of 1 ?M in luciferase assays.2 E2012 also inhibits the activity of the cholesterol synthesis enzyme 3β-hydroxysterol ?24-reductase (DHCR24) in primary rat hepatocytes and HepG2 cells (IC50s = 11 and 15 nM, respectively).3 It reduces Aβ (1-42) (Aβ42) production in primary rat embryonic cerebral cortex neurons with an IC50 value of 220 nM.4 E2012 (100 mg/kg) also decreases Aβ42 levels in guinea pig brain and cerebral spinal fluid (CSF).4
1.Hahn, S., Brüning, T., Ness, J., et al.Presenilin-1 but not amyloid precursor protein mutations present in mouse models of Alzheimer's disease attenuate the response of cultured cells to γ-secretase modulators regardless of their potency and structureJ. Neurochem.116(3)385-395(2011) 2.Dimitrov, M., Alattia, J.-R., Lemmin, T., et al.Alzheimer's disease mutations in APP but not γ-secretase modulators affect epsilon-cleavage-dependent AICD productionNat. Commun.4:2246(2013) 3.Nakano-Ito, K., Fujikawa, Y., Hihara, T., et al.E2012-induced cataract and its predictive biomarkersToxicol. Sci.137(1)249-258(2014) 4.Kimura, T., Kawano, K., Doi, E., et al.Cinnamide compound(2005)
| Cas No. | 870843-42-8 | SDF | |
| 别名 | (E)-1-[(1S)-1-(4-氟苯基)乙基]-3-[3-甲氧基-4-(4-甲基-1H-咪唑-1-YL)亚苄基]哌啶-2-酮 | ||
| Canonical SMILES | O=C(N([C@H](C1=CC=C(C=C1)F)C)CCC/2)C2=C\C3=CC=C(N4C=NC(C)=C4)C(OC)=C3 | ||
| 分子式 | C25H26FN3O2 | 分子量 | 419.49 |
| 溶解度 | DMSO: ≥ 50 mg/mL (119.19 mM) | 储存条件 | Store at -20°C |
| 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 | 2.3838 mL | 11.9192 mL | 23.8385 mL |
| 5 mM | 0.4768 mL | 2.3838 mL | 4.7677 mL |
| 10 mM | 0.2384 mL | 1.1919 mL | 2.3838 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。
Trend of the risk and protective factors of chronic diseases in adolescents, National Adolescent School-based Health Survey (PeNSE 2009 E 2012)
Rev Bras Epidemiol 2014;17 Suppl 1:77-91.PMID:25054255DOI:10.1590/1809-4503201400050007.
Objective: To compare the prevalence of major risk and protection factors for chronic non-communicable diseases in school-aged children in Brazilian capitals surveyed in the National Adolescent School-based Health Survey in its two editions, 2009 and 2012. Methods: The frequencies, with Confidence Interval of 95%, of the following demographic variables were compared: food intake, body image, physical activity, smoking, alcohol and other drugs. Prevalence was compared in the two editions of the survey. Results: The proportion of students who attend two physical education classes a week was maintained at 49% between 2009 and 2012, increasing in public schools from 50.6% (95%CI 49.8 - 51.4) to 52.5% (95%CI 49.2 - 55.7), and decreasing in private schools. There was no change in the proportion of students who watch two hours or more of television daily, about 80%. As for body image, there was no change between the two editions, and about 60% considered themselves being of normal weight. There was a reduction in the percentage of adolescents who experienced cigarettes, from 24.2% (95%CI 23.6 - 24.8) to 22.3% (95%CI 21.4 - 23.2), and the prevalence of smoking was maintained at about 6% (there was no statistical difference between 2009 and 2012). The consumption of beans, fruits, sweets and soft drinks also decreased. Frequency of drug experimentation was of 8.7% (95%CI 8.3 - 9.1) in 2009, and 9.6% (95%CI 9.0 - 10.3) in 2012, with no difference between confidence intervals, and the frequency of alcohol experimentation was maintained at about 70%; the percentage of use in the past 30 days was also maintained at around 27%. Conclusion: In the Brazilian capitals, the vast majority of prevalence of risk factors were kept stable in the two editions of the National Survey of School. These data generate evidence to guide the implementation of public policies to minimize the exposure of adolescents to risk factors.
Temporal analysis of reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012
J Bras Pneumol 2016 Nov-Dec;42(6):416-422.PMID:28117471DOI:10.1590/S1806-37562016000000054.
Objective:: To investigate the reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012. Methods:: This was an observational study based on secondary time series data collected from the Brazilian Case Registry Database for the 2002-2012 period. The incidence of tuberculosis was stratified by gender, age group, geographical region, and outcome, as was that of tuberculosis-HIV co-infection. Results:: Nationally, the incidence of tuberculosis declined by 18%, whereas that of tuberculosis-HIV co-infection increased by 3.8%. There was an overall decrease in the incidence of tuberculosis, despite a significant increase in that of tuberculosis-HIV co-infection in women. The incidence of tuberculosis decreased only in the 0- to 9-year age bracket, remaining stable or increasing in the other age groups. The incidence of tuberculosis-HIV co-infection increased by 209% in the ≥ 60-year age bracket. The incidence of tuberculosis decreased in all geographical regions except the south, whereas that of tuberculosis-HIV co-infection increased by over 150% in the north and northeast. Regarding the outcomes, patients with tuberculosis-HIV co-infection, in comparison with patients infected with tuberculosis only, had a 48% lower chance of cure, a 50% greater risk of treatment nonadherence, and a 94% greater risk of death from tuberculosis. Conclusions:: Our study shows that tuberculosis continues to be a relevant public health issue in Brazil, because the goals for the control and cure of the disease have yet to be achieved. In addition, the sharp increase in the incidence of tuberculosis-HIV co-infection in women, in the elderly, and in the northern/northeastern region reveals that the population of HIV-infected individuals is rapidly becoming more female, older, and more impoverished. Objetivo:: Investigar os casos notificados de tuberculose e de sua coinfecção com o HIV na população brasileira no período entre 2002 E 2012. Métodos:: Realizou-se um estudo observacional de série temporal, no qual foram analisados dados secundários coletados do Sistema de Informação de Agravos de Notificação, no período entre 2002 E 2012. As incidências de tuberculose e tuberculose-HIV foram estratificadas por sexo, faixa etária, macrorregião e situação de encerramento. Resultados:: A incidência de tuberculose decaiu 18%, enquanto a de coinfecção tuberculose-HIV aumentou 3,8% no país. Houve uma redução geral da incidência de tuberculose apesar do aumento expressivo de tuberculose-HIV em mulheres. A taxa de incidência de tuberculose diminuiu apenas na faixa etária de 0-9 anos, permanecendo estável ou com variação positiva nas outras faixas etárias. A incidência da coinfecção tuberculose-HIV cresceu 209% na faixa etária ≥ 60 anos. A incidência de tuberculose diminuiu em todas as macrorregiões, exceto no Sul, enquanto a de tuberculose-HIV aumentou mais de 150% no Norte e Nordeste. Quanto à situação de encerramento, revelou-se que pacientes com tuberculose-HIV têm 48% menos chance de cura, 50% mais chance de abandonar o tratamento e 94% mais chance de óbito por tuberculose em relação àqueles sem a coinfecção. Conclusões:: O presente estudo evidencia a tuberculose como um importante problema de saúde pública no Brasil, uma vez que as metas estabelecidas de cura e controle da doença ainda não foram alcançadas. Ademais, o aumento vertiginoso na incidência de tuberculose-HIV em mulheres, idosos e nas regiões Norte e Nordeste evidencia a feminização, a transição etária e a pauperização pelo HIV.
Analysis of the spatial distribution of dengue cases in the city of Rio de Janeiro, 2011 and 2012
Rev Saude Publica 2017 Aug 17;51:79.PMID:28832752DOI:10.11606/S1518-8787.2017051006239.
Objective: Analyze the spatial distribution of classical dengue and severe dengue cases in the city of Rio de Janeiro. Methods: Exploratory study, considering cases of classical dengue and severe dengue with laboratory confirmation of the infection in the city of Rio de Janeiro during the years 2011/2012. The georeferencing technique was applied for the cases notified in the Notification Increase Information System in the period of 2011 and 2012. For this process, the fields "street" and "number" were used. The ArcGis10 program's Geocoding tool's automatic process was performed. The spatial analysis was done through the kernel density estimator. Results: Kernel density pointed out hotspots for classic dengue that did not coincide geographically with severe dengue and were in or near favelas. The kernel ratio did not show a notable change in the spatial distribution pattern observed in the kernel density analysis. The georeferencing process showed a loss of 41% of classic dengue registries and 17% of severe dengue registries due to the address in the Notification Increase Information System form. Conclusions: The hotspots near the favelas suggest that the social vulnerability of these localities can be an influencing factor for the occurrence of this aggravation since there is a deficiency of the supply and access to essential goods and services for the population. To reduce this vulnerability, interventions must be related to macroeconomic policies. Objetivo: Analisar a distribuição espacial dos casos de dengue clássico e dengue grave no município do Rio de Janeiro. Métodos: Estudo exploratório, considerando casos de dengue clássico e de dengue grave com comprovação laboratorial da infecção, ocorridos no município do Rio de Janeiro nos anos de 2011/2012. Foi aplicada a técnica de georreferenciamento dos casos notificados no Sistema de Informação de Agravos de Notificação, no período de 2011 E 2012. Para esse processo, utilizaram-se os campos "logradouro" e "número". Foi realizado o processo automático da ferramenta Geocoding do programa ArcGis10. A análise espacial foi feita a partir do estimador de densidade Kernel. Resultados: A densidade de Kernel apontou áreas quentes para dengue clássico não coincidente geograficamente a dengue grave, estando localizadas dentro ou próximas de favelas. O cálculo da razão de Kernel não apresentou modificação significativa no padrão de distribuição espacial observados na análise da densidade de Kernel. O processo de georreferenciamento mostrou perda de 41% dos registros de dengue clássico e 17% de dengue grave devido ao endereçamento da ficha do Sistema de Informação de Agravos de Notificação. Conclusões: As áreas quentes próximas às favelas sugerem que a vulnerabilidade social existente nessas localidades pode ser um fator de influência para a ocorrência desse agravo, uma vez que há deficiência da oferta e acesso a bens e serviços essenciais para a população. Para diminuir essa vulnerabilidade, as intervenções devem estar relacionadas a políticas macroeconômicas.
Risk factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil
Rev Saude Publica 2017 Apr 27;51(0):41.PMID:28489185DOI:10.1590/S1518-8787.2017051006688.
Objective: To analyze the prevalence and factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil. Methods: This is a cross-sectional study of cases of tuberculosis tested for first-line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin) in Espírito Santo between 2002 and 2012. We have used laboratory data and registration of cases of tuberculosis - from the Sistema Nacional de Agravos de Notificação and Sistema para Tratamentos Especiais de Tuberculose. Individuals have been classified as resistant and non-resistant and compared in relation to the sociodemographic, clinical, and epidemiological variables. Some variables have been included in a logistic regression model to establish the factors associated with resistance. Results: In the study period, 1,669 individuals underwent anti-tuberculosis drug susceptibility testing. Of these individuals, 10.6% showed resistance to any anti-tuberculosis drug. The rate of multidrug resistance observed, that is, to rifampicin and isoniazid, has been 5%. After multiple analysis, we have identified as independent factors associated with resistant tuberculosis: history of previous treatment of tuberculosis [recurrence (OR = 7.72; 95%CI 4.24-14.05) and re-entry after abandonment (OR = 3.91; 95%CI 1.81-8.43)], smoking (OR = 3.93; 95%CI 1.98-7.79), and positive culture for Mycobacterium tuberculosis at the time of notification of the case (OR = 3.22; 95%CI 1.15-8.99). Conclusions: The partnership between tuberculosis control programs and health teams working in the network of Primary Health Care needs to be strengthened. This would allow the identification and monitoring of individuals with a history of previous treatment of tuberculosis and smoking. Moreover, the expansion of the offer of the culture of tuberculosis and anti-tuberculosis drug susceptibility testing would provide greater diagnostic capacity for the resistant types in Espírito Santo. Objetivo: Analisar a prevalência e fatores associados à tuberculose resistente no Espírito Santo. Métodos: Estudo transversal dos casos de tuberculose testados para fármacos de primeira linha (isoniazida, rifampicina, pirazinamida, etambutol e estreptomicina) no Espírito Santo entre 2002 E 2012. Foram utilizados dados laboratoriais e de registro de casos de tuberculose - Sistema Nacional de Agravos de Notificação e Sistema para Tratamentos Especiais de Tuberculose. Os indivíduos foram classificados em resistentes e não resistentes, e comparados para variáveis sociodemográficas, clínicas e epidemiológicas. Algumas variáveis foram inclusas em um modelo de regressão logística para estabelecimento de fatores associados à resistência. Resultados: No período do estudo, 1.669 indivíduos tiveram o teste de sensibilidade aos fármacos antituberculose realizado. Destes, 10,6% apresentaram resistência a qualquer droga antituberculose. A taxa de multirresistência observada, isto é, à rifampicina e isoniazida, foi de 5%. Após a análise múltipla, foram identificados como fatores associados independentes para tuberculose resistente: história de tratamento prévio para tuberculose [Recidiva (OR = 7,72; IC95% 4,24-14,05) e reingresso após abandono (OR = 3,91; IC95% 1,81-8,43)], tabagismo (OR = 3,93; IC95% 1,98-7,79) e cultura positiva para Mycobacterium tuberculosis no momento da notificação do caso (OR = 3,22; IC95% 1,15-8,99). Conclusões: É necessário o fortalecimento da parceria entre os programas de controle de tuberculose e as equipes de saúde que atuam na rede de Atenção Primária à Saúde. Isso possibilitaria identificar e acompanhar indivíduos com história de tratamento prévio para tuberculose e tabagismo. Além disso, a ampliação da oferta de cultura e Teste de Sensibilidade a fármacos antituberculose proporcionaria maior capacidade diagnóstica para as formas resistentes no Espírito Santo.
Socioeconomic, hygienic, and sanitation factors in reducing diarrhea in the Amazon
Rev Saude Publica 2016 Dec 22;50:77.PMID:28099660DOI:10.1590/S1518-8787.2016050006505.
Objective: To analyze the contributions of the socioeconomic, hygienic, and sanitation improvements in reducing the prevalence of diarrhea in a city of the Amazon. Methods: In this population-based cross-sectional study, we analyzed data from surveys conducted in the city of Jordão, Acre. In 2005 and 2012, these surveys evaluated, respectively, 466 and 826 children under five years old. Questionnaires were applied on the socioeconomic conditions, construction of houses, food and hygienic habits, and environmental sanitation. We applied Pearson's Chi-squared test and Poisson regression to verify the relationship between origin of water, construction of homes, age of introduction of cow's milk in the diet, place of birth and the prevalence of diarrhea. Results: The prevalence of diarrhea was reduced from 45.1% to 35.4%. We identified higher probability of diarrhea in children who did not use water from the public network, in those receiving cow's milk in the first month after birth, and in those living in houses made of paxiúba. Children born at home presented lower risk of diarrhea when compared to those who were born in hospital, with this difference reversing for the 2012 survey. Conclusions: Sanitation conditions improved with the increase of bathrooms with toilets, implementation of the Programa de Saúde da Família (PSF - Family Health Program), and water treatment in the city. The multivariate regression model identified a statistically significant association between use of water from the public network, construction of houses, late introduction of cow's milk, and access to health service with occurrence of diarrhea. Objetivo: Analisar as contribuições das melhorias socioeconômicas, higiênicas e de saneamento na redução da prevalência de diarreia em uma cidade na Amazônia. Métodos: Neste estudo transversal de base populacional, foram analisados dados dos inquéritos realizados no município de Jordão, Acre. Em 2005 E 2012, foram avaliadas, respectivamente, 466 e 826 crianças menores de cinco anos. Foram aplicados questionários sobre as condições socioeconômicas, construção dos domicílios, hábitos higiênicos e alimentares e saneamento ambiental. Foi aplicado o teste Qui-quadrado de Pearson e a Regressão de Poisson para verificar a relação existente entre procedência da água, tipo de construção do domicílio, idade de introdução de leite de vaca na dieta e local de nascimento e a prevalência de diarreia. Resultados: A prevalência de diarreia foi reduzida de 45,1% para 35,4%. Foi identificada maior probabilidade de desenvolvimento de diarreia em crianças que não utilizaram água da rede pública, as que receberam leite de vaca no primeiro mês após o nascimento e as residentes em domicílios de paxiúba. As crianças que nasceram no domicílio apresentaram menor risco de diarreia quando comparadas às que nasceram em hospital, com essa diferença se invertendo para o inquérito de 2012. Conclusões: Ocorreu melhora nas condições de saneamento com aumento no número de banheiro com vasos sanitários, implantação do Programa de Saúde da Família e tratamento de água na sede do município. O modelo de regressão multivariada identificou associação estatisticamente significativa entre utilização de água da rede pública, construção da moradia, introdução tardia de leite de vaca e acesso a serviço de saúde com ocorrência de diarreia.