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[PMID]:28460083
[Au] Autor:Rendas-Baum R; Kosinski M; Singh A; Mebus CA; Wilkinson BE; Wallenstein GV
[Ad] Endereço:QualityMetric Incorporated Lincoln, RI.
[Ti] Título:Estimated medical expenditure and risk of job loss among rheumatoid arthritis patients undergoing tofacitinib treatment: post hoc analyses of two randomized clinical trials.
[So] Source:Rheumatology (Oxford);56(8):1386-1394, 2017 Aug 01.
[Is] ISSN:1462-0332
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: RA causes high disability levels and reduces health-related quality of life, triggering increased costs and risk of unemployment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. These post hoc analyses of phase 3 data aimed to assess monthly medical expenditure (MME) and risk of job loss for tofacitinib treatment vs placebo. Methods: Data analysed were from two randomized phase 3 studies of RA patients (n = 1115) with inadequate response to MTX or TNF inhibitors (TNFi) receiving tofacitinib 5 or 10 mg twice daily, adalimumab (one study only) or placebo, in combination with MTX. Short Form 36 version 2 Health Survey physical and mental component summary scores were translated into predicted MME via an algorithm and concurrent inability to work and job loss risks at 6, 12 and 24 months, using Medical Outcomes Study data. Results: MME reduction by month 3 was $100 greater for tofacitinib- than placebo-treated TNFi inadequate responders (P < 0.001); >20 and 6% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾16%, and risk of future job loss decreased ∼20% (P < 0.001 vs placebo). MME reduction by month 3 was $70 greater for tofacitinib- than placebo-treated MTX inadequate responders (P < 0.001); ⩾23 and 13% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾31% and risk of future job loss decreased ⩾25% (P < 0.001 vs placebo). Conclusion: Tofacitinib treatment had a positive impact on estimated medical expenditure and risk of job loss for RA patients with inadequate response to MTX or TNFi.
[Mh] Termos MeSH primário: Antirreumáticos/economia
Artrite Reumatoide/economia
Efeitos Psicossociais da Doença
Gastos em Saúde
Piperidinas/economia
Pirimidinas/economia
Pirróis/economia
Retorno ao Trabalho/estatística & dados numéricos
[Mh] Termos MeSH secundário: Adalimumab/administração & dosagem
Adalimumab/economia
Adulto
Antirreumáticos/administração & dosagem
Artrite Reumatoide/tratamento farmacológico
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Seres Humanos
Masculino
Metotrexato/administração & dosagem
Metotrexato/economia
Meia-Idade
Piperidinas/administração & dosagem
Pirimidinas/administração & dosagem
Pirróis/administração & dosagem
Fatores de Risco
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antirheumatic Agents); 0 (Piperidines); 0 (Pyrimidines); 0 (Pyrroles); 87LA6FU830 (tofacitinib); FYS6T7F842 (Adalimumab); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/rheumatology/kex087


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[PMID]:28449948
[Au] Autor:Lutz SZ; Ullrich A; Häring HU; Ullrich S; Gerst F
[Ad] Endereço:German Center for Diabetes Research (DZD e.V.), Germany; Institute for Diabetes Research and Metabolic Diseases IDM of the Helmholtz Center Munich at the Eberhard-Karls-University of Tübingen, Germany; University Hospital Tübingen, Internal Medicine IV, Endocrinology, Diabetology, Angiology, Nephrol
[Ti] Título:Sunitinib specifically augments glucose-induced insulin secretion.
[So] Source:Cell Signal;36:91-97, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The tyrosine kinase inhibitor sunitinib is used for the treatment of numerous cancers in humans. In diabetic patients, sunitinib lowers blood glucose levels and improves glycaemic control. This study aims to analyse whether sunitinib has specific and direct effects on insulin secreting ß-cells. Regulation of insulin secretion, of cellular cAMP levels and activation of signalling pathways were examined upon exposure of rat insulinoma INS-1E cells to sunitinib under specific stimulatory and inhibitory conditions. Secreted insulin and cellular cAMP levels were measured using RIA and ELISA, respectively. Protein phosphorylations were examined on western blots. Sunitinib enhanced glucose-induced insulin secretion (GIIS) concentration-dependently, reaching a maximal stimulation at 2µM. Sunitinib further augmented insulin secretion in the presence of elevated cAMP levels and the FFAR1 agonists. Adrenaline and the PKA inhibitor H89 counteracted the stimulatory effect of sunitinib on secretion. However, sunitinib altered neither the cellular levels of cAMP nor the phosphorylation of PKA. Sunitinib did not reduce IGF-1-induced phosphorylation of AKT/PKB and ERK1/2. In conclusion, these results suggest that sunitinib stimulates GIIS by a direct effect on ß-cells, which may contribute to the glucose-lowering action of the tyrosine kinase inhibitor in humans.
[Mh] Termos MeSH primário: Glucose/farmacologia
Indóis/farmacologia
Insulina/secreção
Pirróis/farmacologia
[Mh] Termos MeSH secundário: Compostos de Anilina
Animais
Linhagem Celular
Colforsina/farmacologia
AMP Cíclico/metabolismo
Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Fator de Crescimento Insulin-Like I/metabolismo
Isoquinolinas/farmacologia
Fenilpropionatos
Fosforilação/efeitos dos fármacos
Inibidores de Proteínas Quinases/farmacologia
Ratos
Transdução de Sinais/efeitos dos fármacos
Sulfonamidas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aniline Compounds); 0 (H-89 dihydrochloride hydrate); 0 (Indoles); 0 (Insulin); 0 (Isoquinolines); 0 (Phenylpropionates); 0 (Protein Kinase Inhibitors); 0 (Pyrroles); 0 (Sulfonamides); 0 (TUG-469); 1F7A44V6OU (Colforsin); 67763-96-6 (Insulin-Like Growth Factor I); E0399OZS9N (Cyclic AMP); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); IY9XDZ35W2 (Glucose); V99T50803M (sunitinib)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29335214
[Au] Autor:Poce G; Cocozza M; Alfonso S; Consalvi S; Venditti G; Fernandez-Menendez R; Bates RH; Barros Aguirre D; Ballell L; De Logu A; Vistoli G; Biava M
[Ad] Endereço:Department of Chemistry and Technology of Drugs, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy. Electronic address: giovanna.poce@uniroma1.it.
[Ti] Título:In vivo potent BM635 analogue with improved drug-like properties.
[So] Source:Eur J Med Chem;145:539-550, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:BM635 is the hit compound of a promising anti-TB compound class. Herein we report systematic variations around the central pyrrole core of BM635 and we describe the design, synthesis, biological evaluation, pharmacokinetic analysis, as well as in vivo TB mouse efficacy studies of novel BM635 analogues that show improved physicochemical properties. This hit-to-lead campaign led to the identification of a new analogue, 4-((1-isopropyl-5-(4-isopropylphenyl)-2-methyl-1H-pyrrol-3-yl)methyl)morpholine (17), that shows excellent activity (MIC = 0.15 µM; SI = 133) against drug-sensitive Mycobacterium tuberculosis strains, as well as efficacy in a murine model of TB infection.
[Mh] Termos MeSH primário: Antituberculosos/farmacologia
Mycobacterium tuberculosis/efeitos dos fármacos
Pirróis/farmacologia
Tuberculose/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antituberculosos/síntese química
Antituberculosos/química
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Desenho de Drogas
Células Hep G2
Seres Humanos
Camundongos
Camundongos Endogâmicos C57BL
Testes de Sensibilidade Microbiana
Estrutura Molecular
Pirróis/síntese química
Pirróis/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (BM635 compound); 0 (Pyrroles)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:29335201
[Au] Autor:Gouda AM; El-Ghamry HA; Bawazeer TM; Farghaly TA; Abdalla AN; Aslam A
[Ad] Endereço:Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
[Ti] Título:Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis and cytotoxic screening with potential apoptosis-inducing activity.
[So] Source:Eur J Med Chem;145:350-359, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Two novel series including Schiff bases of the pyrrolizine-5-carboxamides and their Cu(II) complexes were designed, synthesized and analysed using spectral and analytical techniques. The analytical results indicated the formation of the complexes in 1:1 or 1:2 (Metal:Ligand) ratio. The geometry around the Cu centers was confirmed to be tetrahedral or octahedral. The cytotoxic activity of the new compounds was evaluated using MCF-7 (human breast adenocarcinoma), A2780 (human ovary adenocarcinoma) and HT29 (human colon adenocarcinoma), in addition to MRC5 (normal human fetal lung fibroblast) cells using the MTT cytotoxicity assay. The Schiff base 12c and the Cu complex 13b were the most active in the two series with IC values in the range of 0.14-2.54 µM against the three cell lines. Also, the Cu complex 13e showed excellent activity against HT29 with IC = 0.05µM. 7-Cyano-N-(4-methoxyphenyl)-6-((3-phenylallylidene) amino)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (12c) showed high selectivity (6-13 folds) for cancerous cells over normal cells; and it induced marginal increases in the G1 and S phases of MCF-7 cells during cell cycle analysis, while compound 13b increased the MCF-7 Sub-G1 proapoptotic population, and blocked cells in the G2-M phase in a dose dependent manner. The annexin V apoptosis assay revealed the ability of compounds 12c and 13b to increase the early apoptotic MCF-7 cell populations two and three fold, respectively. Furthermore, these findings were supported by data showing that the two compounds (12c and 13b) elicit cytotoxic activity. Taken together, the data presented in this study warrants further in vitro and in vivo investigations.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Complexos de Coordenação/farmacologia
Cobre/farmacologia
Pirróis/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Complexos de Coordenação/síntese química
Complexos de Coordenação/química
Cobre/química
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Estrutura Molecular
Pirróis/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Coordination Complexes); 0 (Pyrroles); 789U1901C5 (Copper)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:29331754
[Au] Autor:Wang W; Xu S; Duan Y; Liu X; Li X; Wang C; Zhao B; Zheng P; Zhu W
[Ad] Endereço:Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, PR China.
[Ti] Título:Synthesis and bioevaluation and doking study of 1H-pyrrolo[2,3-b]pyridine derivatives bearing aromatic hydrazone moiety as c-Met inhibitors.
[So] Source:Eur J Med Chem;145:315-327, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Two series of aromatic hydrazone derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (7a-r, 8a-i, 12a-b, 13a-c, 16a-d and 17a-e) were designed, synthesized and evaluated for the IC values against four cancer cell lines (A549, HepG2, MCF-7and PC-3). Two selected compounds (7c and 17e) were further evaluated for the activity against c-Met, Flt-3, VEGFR-2 and EGFR kinases. The data indicated that targets compounds were selective for c-Met kinase. And the most promising compound 7c was further studied in terms of dose-dependent, time-dependent and cell apoptosis. Most of the compounds showed excellent cytotoxicity activity, especially the most promising compound 7c with the IC values of 0.82 ±â€¯0.08 µM, 1.00 ±â€¯0.11 µM, 0.93 ±â€¯0.28 µM and 0.92 ±â€¯0.17 µM against A549, HepG2, MCF-7 and PC-3 cell lines and 0.506 µM against c-Met kinase. Structure-activity relationships (SARs) and docking studies indicated that the activities of the phenyl hydrazone derivatives (7a-r and 8a-i) were superior to that of the heterocyclic hydrazone series (12a-b, 13a-c, 16a-d and 17a-e). What's more, the further studies indicated that the target compounds can induce apoptosis of A549 cells and arrest efficiently the cell cycle progression in G2/M phase of A549 cells.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Hidrazonas/farmacologia
Simulação de Acoplamento Molecular
Inibidores de Proteínas Quinases/farmacologia
Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores
Piridinas/farmacologia
Pirróis/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Hidrazonas/química
Estrutura Molecular
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Proteínas Proto-Oncogênicas c-met/metabolismo
Piridinas/síntese química
Piridinas/química
Pirróis/síntese química
Pirróis/química
Relação Estrutura-Atividade
Fatores de Tempo
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Hydrazones); 0 (Protein Kinase Inhibitors); 0 (Pyridines); 0 (Pyrroles); EC 2.7.10.1 (Proto-Oncogene Proteins c-met); QX4465NR9T (pyrrolo(2, 3-b)pyridine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE


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[PMID]:28595450
[Au] Autor:Jiang W; Zhou W; Othman R; Uchida H; Watanabe R; Suzuki T; Sakamoto B; Nagai H
[Ad] Endereço:a Department of Ocean Sciences , Tokyo University of Marine Science and Technology , Tokyo , Japan.
[Ti] Título:A new malyngamide from the marine cyanobacterium Moorea producens.
[So] Source:Nat Prod Res;32(1):97-104, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A new malyngamide (1) was isolated along with seven known compounds (2-8) from the marine cyanobacterium Moorea producens collected in Hawaii. Compound 1 represented the first reported malyngamide with a hydroxy moiety at C-7 of the characteristic fatty acid portion of the compound. Compound 1 showed cytotoxicity against L1210 cell line at an IC value of 2.9 mM and lethal toxicity against the shrimp Palaemon paucidens at a LD value of 33.3 mg/kg. The bioactivity of compound 1 was approximately 10-100 times weaker than those of isomalyngamides A and B (3, 4). These results indicated that the methoxy group at C-7 of the fatty acid section confers a degree of bioactivity in malyngamides.
[Mh] Termos MeSH primário: Cianobactérias/química
Lipopeptídeos/química
Lipopeptídeos/farmacologia
[Mh] Termos MeSH secundário: Amidas/química
Amidas/farmacologia
Animais
Organismos Aquáticos/química
Linhagem Celular Tumoral
Leucemia L1210
Espectroscopia de Ressonância Magnética
Camundongos
Estrutura Molecular
Palaemonidae/efeitos dos fármacos
Pirróis/química
Pirróis/farmacologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Lipopeptides); 0 (Pyrroles); 0 (isomalyngamide A); 0 (isomalyngamide B)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170610
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1338282


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[PMID]:29469555
[Au] Autor:Aletaha D; Kerschbaumer A; Smolen JS
[Ad] Endereço:Medical University of Vienna, Vienna, Austria
[Ti] Título:Tofacitinib for Psoriatic Arthritis.
[So] Source:N Engl J Med;378(8):775, 2018 02 22.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Artrite Psoriásica
Pirimidinas
[Mh] Termos MeSH secundário: Piperidinas
Pirróis
[Pt] Tipo de publicação:LETTER; COMMENT
[Nm] Nome de substância:
0 (Piperidines); 0 (Pyrimidines); 0 (Pyrroles); 87LA6FU830 (tofacitinib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180223
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMc1715189


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[PMID]:29466165
[Au] Autor:Mease P; Gladman D
[Ad] Endereço:Swedish Medical Center, Seattle, WA pmease@philipmease.com
[Ti] Título:Tofacitinib for Psoriatic Arthritis.
[So] Source:N Engl J Med;378(8):775-776, 2018 02 22.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Artrite Psoriásica
Pirimidinas
[Mh] Termos MeSH secundário: Antirreumáticos
Artrite Reumatoide
Seres Humanos
Piperidinas
Inibidores de Proteínas Quinases
Pirróis
Resultado do Tratamento
[Pt] Tipo de publicação:LETTER; COMMENT
[Nm] Nome de substância:
0 (Antirheumatic Agents); 0 (Piperidines); 0 (Protein Kinase Inhibitors); 0 (Pyrimidines); 0 (Pyrroles); 87LA6FU830 (tofacitinib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180222
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMc1715189


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[PMID]:29324347
[Au] Autor:He L; Pei H; Zhang C; Shao M; Li D; Tang M; Wang T; Chen X; Xiang M; Chen L
[Ad] Endereço:State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan 610041, PR China.
[Ti] Título:Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as selective Btk inhibitors with improved pharmacokinetic properties for the treatment of rheumatoid arthritis.
[So] Source:Eur J Med Chem;145:96-112, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) and Fcγ receptor (FcR) signaling pathways, which makes it a uniquely attractive target for the treatment of autoimmune diseases, such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H-pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro. Analysis of the structure-activity relationships (SAR) and drug-like profiles led to the discovery of the optimal compound B16. B16 preferentially inhibited Btk (IC = 21.70 ±â€¯0.82 nM) over closely related kinases with moderate selectivity. Cell-based tests also confirmed that B16 significantly inhibited Btk Y223 auto-phosphorylation and PLCγ2 Y1217 phosphorylation. MTT revealed that B16 displayed weak suppression against normal LO2, HEK293 and THP-1 cell lines with IC values over 30 µM. Moreover, B16 showed very weak potential to block the hERG channel (IC = 11.10 µM) in comparison to ibrutinib (IC = 0.97 µM). Owing to its favorable physicochemical properties (ClogP = 2.53, aqueous solubility ≈ 0.1 mg/mL), pharmacokinetic profiles (F = 49.15%, t = 7.02 h) and reasonable CYP450 profile, B16 exhibited potent anti-arthritis activity and similar efficacy to ibrutinib in reducing paw thickness in CIA mice. In conclusion, B16 is a potent, selective and durable inhibitor of Btk and has the potential to a safe and efficacious treatment for arthritis.
[Mh] Termos MeSH primário: Artrite Reumatoide/tratamento farmacológico
Desenho de Drogas
Inibidores de Proteínas Quinases/farmacologia
Proteínas Tirosina Quinases/antagonistas & inibidores
Pirimidinas/farmacologia
Pirróis/farmacologia
[Mh] Termos MeSH secundário: Animais
Artrite Reumatoide/metabolismo
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Cães
Relação Dose-Resposta a Droga
Haplorrinos
Seres Humanos
Camundongos
Microssomos Hepáticos/química
Microssomos Hepáticos/metabolismo
Modelos Moleculares
Estrutura Molecular
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Proteínas Tirosina Quinases/metabolismo
Pirimidinas/síntese química
Pirimidinas/química
Pirróis/síntese química
Pirróis/química
Ratos
Ratos Sprague-Dawley
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (7H-pyrrolo(2,3-d)pyrimidin-4-amine); 0 (Protein Kinase Inhibitors); 0 (Pyrimidines); 0 (Pyrroles); EC 2.7.10.1 (Agammaglobulinaemia tyrosine kinase); EC 2.7.10.1 (Protein-Tyrosine Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE


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[PMID]:28745371
[Au] Autor:Tang S; Ghazvini Zadeh EH; Kim B; Toomey NT; Bondar MV; Belfield KD
[Ad] Endereço:Department of Chemistry, University of Central Florida, Orlando, FL 32816, USA.
[Ti] Título:Protein-induced fluorescence enhancement of two-photon excitable water-soluble diketopyrrolopyrroles.
[So] Source:Org Biomol Chem;15(31):6511-6519, 2017 Aug 09.
[Is] ISSN:1477-0539
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Fluorescent contrast agents are important tools in cell biology and medical imaging due to their high sensitivity and relative availability. Diketopyrrolopyrrole (DPP) derivatives have been recently studied for applications in bioimaging, but certain drawbacks due to their inherent structure have stifled progress towards their widespread implementation. Aggregation caused quenching (ACQ) associated with π-π stacking in relatively rigid extended conjugation systems as well as hydrophobicity of previously reported DPPs make most unsuitable for biological imaging applications. Addressing these deficiencies, we report the synthesis and photophysical characterization of two new water-soluble diketopyrrolopyrole (DPP) probes that exhibit pronounced protein-induced fluorescence enhancement (PIFE) upon binding serum albumin protein. In vitro studies were also performed showing low cytotoxicity for the new DPP probes. Two-photon fluorescence microscopy (2PFM) images were obtained via excitation at 810 nm and emission in the NIR window of biological transparency, illustrating the potential of these compounds as nonlinear optical bioimaging probes.
[Mh] Termos MeSH primário: Corantes Fluorescentes/química
Imagem Óptica/métodos
Pirróis/química
Albumina Sérica/metabolismo
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Fluorescência
Corantes Fluorescentes/síntese química
Corantes Fluorescentes/metabolismo
Corantes Fluorescentes/toxicidade
Células HCT116
Seres Humanos
Microscopia de Fluorescência/métodos
Fótons
Ligação Proteica
Pirróis/síntese química
Pirróis/metabolismo
Pirróis/toxicidade
Solubilidade
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorescent Dyes); 0 (Pyrroles); 0 (Serum Albumin); 059QF0KO0R (Water)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1039/c7ob01397c



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