Base de dados : MEDLINE
Pesquisa : D08.811.682.047.820.450 [Categoria DeCS]
Referências encontradas : 1103 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 111 ir para página                         

  1 / 1103 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29017920
[Au] Autor:Cho J; Yi H; Jang EY; Lee MS; Lee JY; Kang C; Lee CH; Kim K
[Ad] Endereço:Division of Viral Disease Research, Center for Infectious Diseases Research, Korea National Institute of Health, Cheongju, Republic of Korea; Department of Microbiology, Chungbuk National University, Cheongju, Republic of Korea.
[Ti] Título:Mycophenolic mofetil, an alternative antiviral and immunomodulator for the highly pathogenic avian influenza H5N1 virus infection.
[So] Source:Biochem Biophys Res Commun;494(1-2):298-304, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Infection with the highly pathogenic avian influenza H5N1 virus results in a high incidence of mortality in humans. Severe complications from infection are often associated with hypercytokinemia. However, current neuraminidase inhibitors (NAIs) have several limitations including the appearance of oseltamivir-resistant H5N1 virus and the inability to completely ameliorate hyper-immune responses. To overcome these limitations, we evaluated the anti-viral activity of mycophenolic mofetil (MMF) against A/Vietnam/1194/2004 (H5N1) virus infection using MDCK cells and mice. The IC of MMF (0.94 µM) was comparable to that of zanamivir (0.87 µM) in H5N1 virus-infected MDCK cells based on ELISA. Time-course assays demonstrated that MMF completely inhibited H5N1 viral mRNA replication and protein expression for approximately 8 h after the initiation of treatment. In addition, MMF treatment protected 100% of mice, and lung viral titers were substantially reduced. The anti-viral mechanism of MMF against H5N1 virus infection was further confirmed to depend on the inhibition of cellular inosine monophosphate dehydrogenase (IMPDH) by exogenous guanosine, which inhibits viral mRNA and protein expression. Moreover, IL-1ß, IFN-ß, IL-6, and IP-10 mRNA expression levels were significantly downregulated in MDCK cells with MMF treatment. These results indicated that MMF could represent a novel inhibitor of viral replication and a potent immunomodulator for the treatment of H5N1 virus infection.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Fatores Imunológicos/farmacologia
Vírus da Influenza A Subtipo H5N1/efeitos dos fármacos
Ácido Micofenólico/farmacologia
Infecções por Orthomyxoviridae/tratamento farmacológico
Oseltamivir/farmacologia
[Mh] Termos MeSH secundário: Animais
Quimiocina CXCL10/antagonistas & inibidores
Quimiocina CXCL10/genética
Quimiocina CXCL10/imunologia
Embrião de Galinha
Cães
Feminino
Regulação da Expressão Gênica
Interações Hospedeiro-Patógeno/efeitos dos fármacos
IMP Desidrogenase/antagonistas & inibidores
IMP Desidrogenase/genética
IMP Desidrogenase/imunologia
Vírus da Influenza A Subtipo H5N1/crescimento & desenvolvimento
Vírus da Influenza A Subtipo H5N1/patogenicidade
Interferon beta/antagonistas & inibidores
Interferon beta/genética
Interferon beta/imunologia
Interleucina-1beta/antagonistas & inibidores
Interleucina-1beta/genética
Interleucina-1beta/imunologia
Interleucina-6/antagonistas & inibidores
Interleucina-6/genética
Interleucina-6/imunologia
Pulmão/efeitos dos fármacos
Pulmão/imunologia
Pulmão/virologia
Células Madin Darby de Rim Canino
Camundongos
Camundongos Endogâmicos BALB C
Infecções por Orthomyxoviridae/imunologia
Infecções por Orthomyxoviridae/mortalidade
Infecções por Orthomyxoviridae/patologia
RNA Viral/antagonistas & inibidores
RNA Viral/biossíntese
Análise de Sobrevida
Replicação Viral/efeitos dos fármacos
Zanamivir/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Chemokine CXCL10); 0 (Cxcl10 protein, mouse); 0 (IL1B protein, mouse); 0 (Immunologic Factors); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (RNA, Viral); 0 (interleukin-6, mouse); 20O93L6F9H (Oseltamivir); 77238-31-4 (Interferon-beta); EC 1.1.1.205 (IMP Dehydrogenase); HU9DX48N0T (Mycophenolic Acid); L6O3XI777I (Zanamivir)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171012
[St] Status:MEDLINE


  2 / 1103 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28985504
[Au] Autor:Lin R; Mo Y; Zha H; Qu Z; Xie P; Zhu ZJ; Xu Y; Xiong Y; Guan KL
[Ad] Endereço:State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Molecular and Cell Biology Laboratory, Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China. Electronic address: rlin@
[Ti] Título:CLOCK Acetylates ASS1 to Drive Circadian Rhythm of Ureagenesis.
[So] Source:Mol Cell;68(1):198-209.e6, 2017 Oct 05.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In addition to responding to environmental entrainment with diurnal variation, metabolism is also tightly controlled by cell-autonomous circadian clock. Extensive studies have revealed key roles of transcription in circadian control. Post-transcriptional regulation for the rhythmic gating of metabolic enzymes remains elusive. Here, we show that arginine biosynthesis and subsequent ureagenesis are collectively regulated by CLOCK (circadian locomotor output cycles kaput) in circadian rhythms. Facilitated by BMAL1 (brain and muscle Arnt-like protein), CLOCK directly acetylates K165 and K176 of argininosuccinate synthase (ASS1) to inactivate ASS1, which catalyzes the rate-limiting step of arginine biosynthesis. ASS1 acetylation by CLOCK exhibits circadian oscillation in human cells and mouse liver, possibly caused by rhythmic interaction between CLOCK and ASS1, leading to the circadian regulation of ASS1 and ureagenesis. Furthermore, we also identified NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 (NDUFA9) and inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) as acetylation substrates of CLOCK. Taken together, CLOCK modulates metabolic rhythmicity by acting as a rhythmic acetyl-transferase for metabolic enzymes.
[Mh] Termos MeSH primário: Fatores de Transcrição ARNTL/genética
Argininossuccinato Sintase/genética
Proteínas CLOCK/genética
Ritmo Circadiano/genética
Processamento de Proteína Pós-Traducional
Ureia/metabolismo
[Mh] Termos MeSH secundário: Fatores de Transcrição ARNTL/metabolismo
Acetilação
Animais
Arginina/biossíntese
Argininossuccinato Sintase/metabolismo
Proteínas CLOCK/metabolismo
Linhagem Celular Tumoral
Relógios Circadianos
Complexo I de Transporte de Elétrons/genética
Complexo I de Transporte de Elétrons/metabolismo
Células HEK293
Hepatócitos/citologia
Hepatócitos/metabolismo
Seres Humanos
IMP Desidrogenase/genética
IMP Desidrogenase/metabolismo
Masculino
Camundongos
Camundongos Knockout
Osteoblastos/metabolismo
Osteoblastos/patologia
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ARNTL Transcription Factors); 0 (Arntl protein, mouse); 8W8T17847W (Urea); 94ZLA3W45F (Arginine); EC 1.1.1.205 (IMP Dehydrogenase); EC 1.1.1.205 (IMPDH2 protein, human); EC 1.6.5.3 (Electron Transport Complex I); EC 1.6.5.3 (NDUFA9 protein, human); EC 2.3.1.48 (CLOCK Proteins); EC 2.3.1.48 (Clock protein, mouse); EC 6.3.4.5 (Argininosuccinate Synthase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE


  3 / 1103 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28674185
[Au] Autor:Merran J; Corden JL
[Ad] Endereço:Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
[Ti] Título:Yeast RNA-Binding Protein Nab3 Regulates Genes Involved in Nitrogen Metabolism.
[So] Source:Mol Cell Biol;37(18), 2017 Sep 15.
[Is] ISSN:1098-5549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Termination of RNA polymerase II (Pol II) transcripts occurs through two alternative pathways. Termination of mRNAs is coupled to cleavage and polyadenylation while noncoding transcripts are terminated through the Nrd1-Nab3-Sen1 (NNS) pathway in a process that is linked to RNA degradation by the nuclear exosome. Some mRNA transcripts are also attenuated through premature termination directed by the NNS complex. In this paper we present the results of nuclear depletion of the NNS component Nab3. As expected, many noncoding RNAs fail to terminate properly. In addition, we observe that nitrogen catabolite-repressed genes are upregulated by Nab3 depletion.
[Mh] Termos MeSH primário: Nitrogênio/metabolismo
Proteínas Nucleares/metabolismo
RNA Polimerase II/genética
RNA Mensageiro/genética
RNA Nucleolar Pequeno/genética
Proteínas de Ligação a RNA/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
Terminação da Transcrição Genética/fisiologia
[Mh] Termos MeSH secundário: Repressão Catabólica/genética
Códon sem Sentido/genética
Proteínas de Transporte de Glutamato da Membrana Plasmática/genética
Glutamato-Amônia Ligase/antagonistas & inibidores
Glutamato-Amônia Ligase/metabolismo
IMP Desidrogenase/biossíntese
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon, Nonsense); 0 (Glutamate Plasma Membrane Transport Proteins); 0 (NAB3 protein, S cerevisiae); 0 (Nuclear Proteins); 0 (RNA, Messenger); 0 (RNA, Small Nucleolar); 0 (RNA-Binding Proteins); 0 (Saccharomyces cerevisiae Proteins); EC 1.1.1.205 (IMD2 protein, S cerevisiae); EC 1.1.1.205 (IMP Dehydrogenase); EC 2.7.7.- (RNA Polymerase II); EC 6.3.1.2 (Glutamate-Ammonia Ligase); N762921K75 (Nitrogen)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE


  4 / 1103 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28619817
[Au] Autor:Rives-Quinto N; Franco M; de Torres-Jurado A; Carmena A
[Ad] Endereço:Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas/Universidad Miguel Hernández, 03550 Sant Joan d'Alacant, Alicante, Spain.
[Ti] Título:Synergism between and mutations causes tumor-like overgrowth via Ras activation in neural stem cells and epithelia.
[So] Source:Development;144(14):2570-2583, 2017 07 15.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Over the past decade an intriguing connection between asymmetric cell division, stem cells and tumorigenesis has emerged. Neuroblasts, which are the neural stem cells of the central nervous system, divide asymmetrically and constitute an excellent paradigm for investigating this connection further. Here we show that the simultaneous loss of the asymmetric cell division regulators Canoe (afadin in mammals) and Scribble in neuroblast clones leads to tumor-like overgrowth through both a severe disruption of the asymmetric cell division process and loss-mediated Ras-PI3K-Akt activation. Moreover, loss also interacts synergistically with loss to promote overgrowth in epithelial tissues, here just by activating the Ras-Raf-MAPK pathway. and , which are functionally related to , contribute to repress the Ras-MAPK signaling cascade in epithelia. Hence, our work uncovers novel cooperative interactions between all these well-conserved tumor suppressors that ensure tight regulation of the Ras signaling pathway.
[Mh] Termos MeSH primário: Proteínas de Drosophila/genética
Proteínas de Drosophila/metabolismo
IMP Desidrogenase/metabolismo
Proteínas de Membrana/genética
Mutação
Células-Tronco Neurais/citologia
Células-Tronco Neurais/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Apoptose
Divisão Celular Assimétrica/genética
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/metabolismo
Transformação Celular Neoplásica/patologia
Proteínas de Drosophila/deficiência
Drosophila melanogaster/citologia
Drosophila melanogaster/genética
Drosophila melanogaster/metabolismo
Células Epiteliais/citologia
Células Epiteliais/metabolismo
Feminino
Técnicas de Inativação de Genes
Genes de Insetos
IMP Desidrogenase/genética
Sistema de Sinalização das MAP Quinases
Masculino
Proteínas de Membrana/deficiência
Proteínas de Membrana/metabolismo
Modelos Biológicos
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (Membrane Proteins); 0 (Scribble protein, Drosophila); 0 (canoe protein, Drosophila); EC 1.1.1.205 (IMP Dehydrogenase); EC 1.1.1.205 (raspberry protein, Drosophila)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE
[do] DOI:10.1242/dev.148171


  5 / 1103 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28599189
[Au] Autor:Yang H; Fang Z; Wei Y; Bohannan ZS; Gañán-Gómez I; Pierola AA; Paradiso LJ; Iwamura H; Garcia-Manero G
[Ad] Endereço:Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
[Ti] Título:Preclinical activity of FF-10501-01, a novel inosine-5'-monophosphate dehydrogenase inhibitor, in acute myeloid leukemia.
[So] Source:Leuk Res;59:85-92, 2017 Aug.
[Is] ISSN:1873-5835
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: FF-10501-01 is a selective inosine monophosphate dehydrogenase (IMPDH) inhibitor that has shown activity in cancer cell lines. We studied whether FF-10501-01 is effective in targeting a variety of hypomethylating agent (HMA)-sensitive and -resistant acute myelogenous leukemia (AML) cell lines. METHODS: We treated multiple cell lines (including HMA-resistant cells) with FF-10501-01 and analyzed proliferation, apoptosis, and cell cycle status. We also assessed HMA-FF-10501-01 combinations and the ability of extracellular guanosine to rescue cell proliferation in FF-10501-01-treated cells. We performed high-performance liquid chromatography (HPLC) to study guanine nucleotide levels in treated and untreated cells. Finally, we studied the effects of FF-10501-01 in fresh peripheral blood cells taken from AML patients. RESULTS: FF-10501-01 showed a strong dose-dependent effect on proliferation and induced apoptosis at approximately 30µM. The effects of FF-10501-01 treatment on cell cycle status were variable, with no statistically significant trends. Guanosine rescued proliferation in FF-10501-01-treated cells, and HPLC results showed significant decreases in phosphorylated guanosine levels in MOLM13 cells. FF-10501-01 effectively reduced proliferation at concentrations of 300µM and above in 3 primary AML samples. CONCLUSIONS: FF-10501-01 effectively induces AML cell death and reduces AML peripheral blood cell proliferation by targeting guanine nucleotide biosynthesis regardless of HMA resistance status.
[Mh] Termos MeSH primário: IMP Desidrogenase/antagonistas & inibidores
Leucemia Mieloide Aguda/tratamento farmacológico
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Avaliação Pré-Clínica de Medicamentos
Resistência a Medicamentos Antineoplásicos
Inibidores Enzimáticos/farmacologia
Inibidores Enzimáticos/uso terapêutico
Guanina/biossíntese
Guanina/farmacologia
Seres Humanos
Leucemia Mieloide Aguda/patologia
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 5Z93L87A1R (Guanine); EC 1.1.1.205 (IMP Dehydrogenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170610
[St] Status:MEDLINE


  6 / 1103 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28298229
[Au] Autor:Hu J; Ma L; Wang H; Yan H; Zhang D; Li Z; Jiang J; Li Y
[Ad] Endereço:Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
[Ti] Título:A novel benzo-heterocyclic amine derivative N30 inhibits influenza virus replication by depression of Inosine-5'-Monophospate Dehydrogenase activity.
[So] Source:Virol J;14(1):55, 2017 Mar 15.
[Is] ISSN:1743-422X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUD: Influenza virus is still a huge threat to the world-wide public health. Host inosine-5'- monophosphate dehydrogenase (IMPDH) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. Herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative N30, which was designed to inhibit IMPDH. RESULTS: The results demonstrated that N30 inhibited the replication of H1N1, H3N2, influenza B viruses, including oseltamivir and amantadine resistant strains in vitro. Mechanistically, neuraminidase inhibition assay and hemagglutination inhibition assay suggested that N30 did not directly target the two envelope glycoproteins required for viral adsorption or release. Instead, the compound could depress the activity of IMPDH type II. Based on these findings, we further confirmed that N30 provided a strong inhibition on the replication of respiratory syncytial virus, coronavirus, enterovirus 71 and a diverse strains of coxsackie B virus. CONCLUSIONS: We identified the small molecule N30, as an inhibitor of IMPDH, might be a potential candidate to inhibit the replication of various viruses.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Inibidores Enzimáticos/farmacologia
IMP Desidrogenase/antagonistas & inibidores
Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos
Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos
Vírus da Influenza B/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Aminas/farmacologia
Animais
Linhagem Celular
Coronavirus/efeitos dos fármacos
Enterovirus Humano A/efeitos dos fármacos
Enterovirus Humano B/efeitos dos fármacos
Compostos Heterocíclicos/farmacologia
Seres Humanos
Vírus da Influenza A Subtipo H1N1/fisiologia
Vírus da Influenza A Subtipo H3N2/fisiologia
Vírus da Influenza B/fisiologia
Vírus Sinciciais Respiratórios/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amines); 0 (Antiviral Agents); 0 (Enzyme Inhibitors); 0 (Heterocyclic Compounds); EC 1.1.1.205 (IMP Dehydrogenase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1186/s12985-017-0724-6


  7 / 1103 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28110955
[Au] Autor:Beringer A; Citterio-Quentin A; Otero RO; Gustin C; Clarke R; Salvi JP; Boulieu R
[Ad] Endereço:Université de Lyon, Université Lyon 1, UMR CNRS 5305, Pharmacie Clinique, Pharmacocinétique et Evaluation du Médicament, Lyon, France; Hospices Civils de Lyon, Groupement Hospitalier Edouard Herriot, Laboratoire de Biologie Médicale Multi Sites du CHU de Lyon, unité de Pharmacocinétique Clinique, Ly
[Ti] Título:Determination of inosine 5'-monophosphate dehydrogenase activity in red blood cells of thiopurine-treated patients using HPLC.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1044-1045:194-199, 2017 Feb 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Thiopurine drugs are commonly used in immune diseases and to a lesser extent, in transplant rejection prophylaxis: however interindividual variability in drug response and in the occurrence of adverse events is observed. Genetic variation in thiopurine S-methyltransferase (TPMT) doesn't completely explain the occurrence of all adverse events and drug response variability. The potential implication of other enzymes involved in thiopurine metabolism, such as ITPA, has been investigated over the last decade but little data is available on inosine 5'-monophosphate dehydrogenase (IMPDH) in patients treated with thiopurine drugs. The authors reported a HPLC method to determine IMPDH activity in the red blood cells (RBCs) of thiopurine-treated patients. IMPDH activity was evaluated by enzymatic conversion of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP). The XMP formed was analyzed on a Luna NH stationary phase, a weak anion exchange phase that exhibits both ionic and hydrophobic properties. XMP was eluted below 15min. Intra-assay and inter-assay precisions were below 9% for RBCs supplemented with 2, 40 and 80µmol/L of XMP. IMPDH activity was measured in adults without thiopurine treatment as well as in adult and paediatric patients treated with thiopurines. A wide interindividual variability in IMPDH activity in RBCs was observed. No difference in IMPDH activity was found between untreated subjects and adult and paediatric patients on thiopurine therapy (median value 11.8, 7.9 and 7.7nmol XPM/g Hb/h respectively). The method described is useful in the determination of IMPDH phenotype from patients on thiopurine therapy and in the investigation of the potential relationship between IMPDH activity in RBCs and the occurrence of adverse events and drug response variability.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Eritrócitos/enzimologia
Eritrócitos/metabolismo
IMP Desidrogenase/análise
IMP Desidrogenase/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Criança
Pré-Escolar
Feminino
Seres Humanos
Modelos Lineares
Masculino
Meia-Idade
Purinas/análise
Purinas/metabolismo
Reprodutibilidade dos Testes
Ribonucleotídeos/análise
Ribonucleotídeos/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Purines); 0 (Ribonucleotides); 523-98-8 (xanthosine monophosphate); EC 1.1.1.205 (IMP Dehydrogenase)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170324
[Lr] Data última revisão:
170324
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170124
[St] Status:MEDLINE


  8 / 1103 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28074661
[Au] Autor:Cuny GD; Suebsuwong C; Ray SS
[Ad] Endereço:a Department of Pharmacological and Pharmaceutical Sciences , University of Houston , Houston , TX , USA.
[Ti] Título:Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors: a patent and scientific literature review (2002-2016).
[So] Source:Expert Opin Ther Pat;27(6):677-690, 2017 Jun.
[Is] ISSN:1744-7674
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Inosine-5'-monophosphate dehydrogenase (IMPDH) is an enzyme involved in the de novo biosynthesis of guanine nucleotides. To date human IMPDH inhibitors have been approved for prevention of organ transplant rejection and as anti-viral agents. More recently, the use of IMPDH inhibitors for other indications including cancer and pathogenic microorganisms has been pursued. Areas covered: IMPDH inhibitors disclosed primarily in the patent and scientific literature from 2002 to the present are discussed. Several interesting chemotypes that have not been pursued by patent protection are also highlighted. Expert opinion: Progress has been made in the development of IMPDH inhibitors, particularly compounds that are structurally distinct from mycophenolic acid and nucleoside-based inhibitors. However, clinical progression has been hampered primarily by a limited understanding of the enzyme's role in disease pathophysiology. Finally, most of the IMPDH inhibitors developed over the past fourteen years fall within a relatively narrow set of chemotypes. This provides opportunities for expanding IMPDH inhibitor chemical space to further evaluate this class of molecular targets.
[Mh] Termos MeSH primário: Desenho de Drogas
Inibidores Enzimáticos/farmacologia
IMP Desidrogenase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Antivirais/farmacologia
Antivirais/uso terapêutico
Inibidores Enzimáticos/uso terapêutico
Rejeição de Enxerto/prevenção & controle
Seres Humanos
IMP Desidrogenase/metabolismo
Terapia de Alvo Molecular
Neoplasias/tratamento farmacológico
Neoplasias/patologia
Patentes como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Enzyme Inhibitors); EC 1.1.1.205 (IMP Dehydrogenase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE
[do] DOI:10.1080/13543776.2017.1280463


  9 / 1103 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27847171
[Au] Autor:Chinthakindi PK; Singh J; Gupta S; Nargotra A; Mahajan P; Kaul A; Ahmed Z; Koul S; Sangwan PL
[Ad] Endereço:Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban, 4041, South Africa.
[Ti] Título:Synthesis of α-santonin derivatives for diminutive effect on T and B-cell proliferation and their structure activity relationships.
[So] Source:Eur J Med Chem;127:1047-1058, 2017 Feb 15.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A new library of 20 compounds from α-santonin was synthesized and tested against Con-A induced T-cell proliferation and LPS-induced B-cell proliferation via MTT assay. The study resulted in the identification of potent immunosuppressant molecules, which were further screened along with α-santonin for Tumor Necrosis Factor Alpha (TNF-α) inhibitory activity. One of the molecules (7) at 10 µM showed equipotency to that of dexamethasone (1 µM conc.) used as a standard. Structure activity relationships of the synthesized compounds along with our earlier reported α-santonin derivatives have been studied. Inferences from the modifications carried out at all the three sites of α-santonin have been elaborated. Computational study of the active compounds shows TNF-α protein as its preferable target rather than Inosine Monophosphate Dehydrogenase (IMPDH).
[Mh] Termos MeSH primário: Linfócitos B/citologia
Linfócitos B/efeitos dos fármacos
Santonina/síntese química
Santonina/farmacologia
Linfócitos T/citologia
Linfócitos T/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linfócitos B/metabolismo
Proliferação Celular/efeitos dos fármacos
Técnicas de Química Sintética
IMP Desidrogenase/química
IMP Desidrogenase/metabolismo
Camundongos
Simulação de Acoplamento Molecular
Conformação Proteica
Santonina/química
Santonina/metabolismo
Relação Estrutura-Atividade
Linfócitos T/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tumor Necrosis Factor-alpha); 1VL8J38ERO (Santonin); EC 1.1.1.205 (IMP Dehydrogenase)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170221
[Lr] Data última revisão:
170221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161117
[St] Status:MEDLINE


  10 / 1103 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27818246
[Au] Autor:Isakovic AM; Dulovic M; Markovic I; Kravic-Stevovic T; Bumbasirevic V; Trajkovic V; Isakovic A
[Ad] Endereço:Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Pasterova 2, Belgrade, Serbia.
[Ti] Título:Autophagy suppression sensitizes glioma cells to IMP dehydrogenase inhibition-induced apoptotic death.
[So] Source:Exp Cell Res;350(1):32-40, 2017 Jan 01.
[Is] ISSN:1090-2422
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We investigated the role of autophagy, a process of controlled self-digestion, in the in vitro anticancer action of the inosine monophosphate dehydrogenase (IMPDH) inhibitor ribavirin. Ribavirin-triggered oxidative stress, caspase activation, and apoptotic death in U251 human glioma cells were associated with the induction of autophagy, as confirmed by intracellular acidification, appearance of autophagic vesicles, conversion of microtubule associated protein 1 light chain 3 (LC3)-I to autophagosome-associated LC3-II, and degradation of autophagic target p62/sequestosome 1. Ribavirin downregulated the activity of autophagy-inhibiting mammalian target of rapamycin complex 1 (mTORC1), as indicated by a decrease in phosphorylation of the mTORC1 substrate ribosomal p70S6 kinase and reduction of the mTORC1-activating Src/Akt signaling. Guanosine supplementation inhibited, while IMPDH inhibitor tiazofurin mimicked ribavirin-mediated autophagy induction, suggesting the involvement of IMPDH blockade in the observed effect. Autophagy suppression by ammonium chloride, bafilomycin A1, or RNA interference-mediated knockdown of LC3 sensitized glioma cells to ribavirin-induced apoptosis. Ribavirin also induced cytoprotective autophagy associated with Akt/mTORC1 inhibition in C6 rat glioma cells. Our data demonstrate that ribavirin-triggered Akt/mTORC1-dependent autophagy counteracts apoptotic death of glioma cells, indicating autophagy suppression as a plausible therapeutic strategy for sensitization of cancer cells to IMPDH inhibition.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Autofagia/efeitos dos fármacos
Glioma/enzimologia
IMP Desidrogenase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Inibidores Enzimáticos/farmacologia
Glioma/genética
Glioma/patologia
Seres Humanos
Fosforilação
Proteínas Proto-Oncogênicas c-akt/metabolismo
Interferência de RNA
Ribavirina/análogos & derivados
Ribavirina/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 49717AWG6K (Ribavirin); EC 1.1.1.205 (IMP Dehydrogenase); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); ULJ82834RE (tiazofurin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161108
[St] Status:MEDLINE



página 1 de 111 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde