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[PMID]:29272750
[Au] Autor:Galibert M; Wartenberg M; Lecaille F; Saidi A; Mavel S; Joulin-Giet A; Korkmaz B; Brömme D; Aucagne V; Delmas AF; Lalmanach G
[Ad] Endereço:CNRS UPR 4301, Centre de Biophysique Moléculaire, Rue Charles Sadron, Orléans, France.
[Ti] Título:Substrate-derived triazolo- and azapeptides as inhibitors of cathepsins K and S.
[So] Source:Eur J Med Chem;144:201-210, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Cathepsin (Cat) K is a critical bone-resorbing protease and is a relevant target for the treatment of osteoporosis and bone metastasis, while CatS is an attractive target for drugs in autoimmune diseases (e.g. rheumatoid arthritis), emphysema or neuropathic pain. Despite major achievements, current pharmacological inhibitors are still lacking in safety and may have damaging side effects. A promising strategy for developing safer reversible and competitive inhibitors as new lead compounds could be to insert non-cleavable bonds at the scissile P1-P1' position of selective substrates of CatS and CatK. Accordingly, we introduced a 1,4-disubstituted 1,2,3-triazole heterocycle that mimics most of the features of a trans-amide bond, or we incorporated a semicarbazide bond (azaGly residue) by replacing the α-carbon of the glycyl residue at P1 by a nitrogen atom. AzaGly-containing peptidomimetics inhibited powerfully their respective target proteases in the nM range, while triazolopeptides were weaker inhibitors (Ki in the µM range). The selectivity of the azaGly CatS inhibitor (1b) was confirmed by using spleen lysates from wild-type vs CatS-deficient mice. Alternatively, the azaGly bradykinin-derived CatK inhibitor (2b) potently inhibited CatK (Ki = 9 nM) and impaired its kininase activity in vitro. Molecular modeling studies support that the semicarbazide bond of 2b is more favorable than the 1,2,3-triazole linkage of the bradykinin-derived pseudopeptide 2a to preserve an effective affinity towards CatK, its protease target.
[Mh] Termos MeSH primário: Catepsina K/antagonistas & inibidores
Catepsinas/antagonistas & inibidores
Inibidores de Proteases/química
Inibidores de Proteases/farmacologia
Triazóis/química
Triazóis/farmacologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Catepsina K/metabolismo
Catepsinas/metabolismo
Seres Humanos
Camundongos Endogâmicos C57BL
Simulação de Acoplamento Molecular
Peptídeos/química
Peptídeos/farmacologia
Peptidomiméticos/química
Peptidomiméticos/farmacologia
Relação Estrutura-Atividade
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptides); 0 (Peptidomimetics); 0 (Protease Inhibitors); 0 (Triazoles); EC 3.4.- (Cathepsins); EC 3.4.22.27 (cathepsin S); EC 3.4.22.38 (Cathepsin K)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE


  2 / 22350 MEDLINE  
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[PMID]:29318298
[Au] Autor:Jukic M; Grabrijan K; Kadic S; Lera Garrido FJ; Sosic I; Gobec S; Obreza A
[Ti] Título:Chlorocarbonylsulfenyl Chloride Cyclizations Towards Piperidin-3-yl-oxathiazol-2-ones as Potential Covalent Inhibitors of Threonine Proteases.
[So] Source:Acta Chim Slov;64(4):771-781, 2017 Dec.
[Is] ISSN:1318-0207
[Cp] País de publicação:Slovenia
[La] Idioma:eng
[Ab] Resumo:Using rescaffolding approach, we designed piperidine compounds decorated with an electrophilic oxathiazol-2-one moiety that is known to confer selectivity towards threonine proteases. Our efforts to prepare products according to the published procedures were not successful. Furthermore we identified major side products containing nitrile functional group, resulting from carboxamide dehydration. We systematically optimized reaction conditions towards our desired products to identify heating of carboxamides with chlorocarbonylsulfenyl chloride and sodium carbonate as base in dioxane at 100 °C. Our efforts culminated in the preparation of a small series of piperidin-3-yl-oxathiazol-2-ones that are suitable for further biological evaluation.
[Mh] Termos MeSH primário: Piperidinas/química
Inibidores de Proteases/síntese química
Tiazóis/química
Treonina/metabolismo
[Mh] Termos MeSH secundário: Ciclização
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Piperidines); 0 (Protease Inhibitors); 0 (Thiazoles); 2ZD004190S (Threonine)
[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:180111
[St] Status:MEDLINE


  3 / 22350 MEDLINE  
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[PMID]:29480838
[Au] Autor:Cheng Y; Nickman NA; Jamjian C; Stevens V; Zhang Y; Sauer B; LaFleur J
[Ad] Endereço:Biomedical Informatics Center, George Washington University, Washington, DC.
[Ti] Título:Predicting poor adherence to antiretroviral therapy among treatment-naïve veterans infected with human immunodeficiency virus.
[So] Source:Medicine (Baltimore);97(2):e9495, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Previous studies suggested that human immunodeficiency virus (HIV) infected patients at risk of poor adherence were not distinguishable only based on the baseline characteristics. This study is to identify patient characteristics that would be consistently associated with poor adherence across regimens and to understand the associations between initial and long-term adherence. HIV treatment-naïve patients initiated on protease inhibitors, nonnucleoside reverse transcriptase inhibitors, or integrase strand transfer inhibitors were identified from the Veteran Health Administration system. Initial adherence measured as initial coverage ratio (ICR) and long-term adherence measured as thereafter 1-year proportion days covered (PDC) of base agent and complete regimen were estimated for each patient. The patients most likely to exhibit poor adherence were African-American, with lower socioeconomic status, and healthier. The initial coverage ratio of base agent and complete regimen were highly correlated, but the correlations between ICR and thereafter 1-year PDC were low. However, including initial adherence as a predictor in predictive model would substantially increase predictive accuracy of future adherence.
[Mh] Termos MeSH primário: Infecções por HIV/tratamento farmacológico
Inibidores de Integrase de HIV/uso terapêutico
Adesão à Medicação
Inibidores de Proteases/uso terapêutico
Inibidores da Transcriptase Reversa/uso terapêutico
[Mh] Termos MeSH secundário: Análise de Variância
Feminino
Infecções por HIV/diagnóstico
Infecções por HIV/epidemiologia
Integrase de HIV
Nível de Saúde
Seres Humanos
Modelos Logísticos
Masculino
Meia-Idade
Prognóstico
Estudos Retrospectivos
Fatores de Risco
Fatores Socioeconômicos
Estados Unidos
United States Department of Veterans Affairs
Veteranos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIV Integrase Inhibitors); 0 (Protease Inhibitors); 0 (Reverse Transcriptase Inhibitors); EC 2.7.7.- (HIV Integrase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180227
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009495


  4 / 22350 MEDLINE  
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[PMID]:28461069
[Au] Autor:Shiryaev SA; Farhy C; Pinto A; Huang CT; Simonetti N; Elong Ngono A; Dewing A; Shresta S; Pinkerton AB; Cieplak P; Strongin AY; Terskikh AV
[Ad] Endereço:Sanford-Burnham-Prebys Medical Discovery Institute, Center for Neuroscience, Aging, and Stem Cell Research, La Jolla, CA 92037, United States.
[Ti] Título:Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists.
[So] Source:Antiviral Res;143:218-229, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The recent re-emergence of Zika virus (ZIKV) , a member of the Flaviviridae family, has become a global emergency. Currently, there are no effective methods of preventing or treating ZIKV infection, which causes severe neuroimmunopathology and is particularly harmful to the developing fetuses of infected pregnant women. However, the pathology induced by ZIKV is unique among flaviviruses, and knowledge of the biology of other family members cannot easily be extrapolated to ZIKV. Thus, structure-function studies of ZIKV proteins are urgently needed to facilitate the development of effective preventative and therapeutic agents. Like other flaviviruses, ZIKV expresses an NS2B-NS3 protease, which consists of the NS2B cofactor and the NS3 protease domain and is essential for cleavage of the ZIKV polyprotein precursor and generation of fully functional viral proteins. Here, we report the enzymatic characterization of ZIKV protease, and we identify structural scaffolds for allosteric small-molecule inhibitors of this protease. Molecular modeling of the protease-inhibitor complexes suggests that these compounds bind to the druggable cavity in the NS2B-NS3 protease interface and affect productive interactions of the protease domain with its cofactor. The most potent compound demonstrated efficient inhibition of ZIKV propagation in vitro in human fetal neural progenitor cells and in vivo in SJL mice. The inhibitory scaffolds could be further developed into valuable research reagents and, ultimately, provide a roadmap for the selection of efficient inhibitors of ZIKV infection.
[Mh] Termos MeSH primário: Sítio Alostérico
Inibidores de Proteases/química
Inibidores de Proteases/farmacologia
Proteínas não Estruturais Virais/química
Zika virus/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antivirais/antagonistas & inibidores
Antivirais/química
Sequência de Bases
Ativação Enzimática
Feminino
Flavivirus/química
Expressão Gênica
Seres Humanos
Concentração Inibidora 50
Camundongos
Modelos Moleculares
Ligação Proteica
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
RNA Helicases/química
RNA Helicases/efeitos dos fármacos
Fatores de Transcrição SOXB1/genética
Alinhamento de Sequência
Serina Endopeptidases/química
Serina Endopeptidases/efeitos dos fármacos
Células-Tronco
Proteínas não Estruturais Virais/efeitos dos fármacos
Proteínas Virais/química
Proteínas Virais/genética
Zika virus/química
Zika virus/genética
Zika virus/crescimento & desenvolvimento
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (NS2B protein, flavivirus); 0 (NS3 protein, flavivirus); 0 (Protease Inhibitors); 0 (SOX2 protein, human); 0 (SOXB1 Transcription Factors); 0 (Viral Nonstructural Proteins); 0 (Viral Proteins); EC 3.4.21.- (Serine Endopeptidases); EC 3.6.4.13 (RNA Helicases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  5 / 22350 MEDLINE  
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[PMID]:28467359
[Au] Autor:Yoshida K; Hai H; Tamori A; Teranishi Y; Kozuka R; Motoyama H; Kawamura E; Hagihara A; Uchida-Kobayashi S; Morikawa H; Enomoto M; Murakami Y; Kawada N
[Ad] Endereço:Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan. m2028081@med.osaka-cu.ac.jp.
[Ti] Título:Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed.
[So] Source:Int J Mol Sci;18(5), 2017 May 03.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:We evaluated the transition of dominant resistance-associated substitutions (RASs) in hepatitis C virus during long-term follow-up after the failure of DAAs (direct acting antivirals)-based therapy. RASs in non-structure (NS)3/4A, NS5A, NS5B, and deletions in NS5A from 20 patients who failed simeprevir/pegylated-interferon/ribavirin (SMV/PEG-IFN/RBV) and 25 patients who failed daclatasvir/asunaprevir (DCV/ASV) treatment were examined by direct sequencing. With respect to SMV/PEG-IFN/RBV treatment, RAS was detected at D168 in NS3/4A but not detected in NS5A and NS5B at treatment failure in 16 of 20 patients. During the median follow-up period of 64 weeks, the RAS at D168 became less dominant in 9 of 16 patients. Among 25 DCV/ASV failures, RASs at D168, L31, and Y93 were found in 57.1%, 72.2%, and 76.9%, respectively. NS5A deletions were detected in 3 of 10 patients treated previously with SMV/PEG-IFN/RBV. The number of RASs in the breakthrough patients exceeded that in relapsers (mean 3.9 vs. 2.7, < 0.05). RAS at D168 in NS3/4A became less dominant in 6 of 15 patients within 80 weeks. Y93H emerged at the time of relapse, then decreased gradually by 99% at 130 weeks post-treatment. Emerged RASs were associated with the clinical course of treatment and could not be detected during longer follow-up.
[Mh] Termos MeSH primário: Farmacorresistência Viral/genética
Hepacivirus/genética
Hepatite C Crônica/tratamento farmacológico
Serina Proteases/genética
Proteínas não Estruturais Virais/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Antivirais/farmacologia
Antivirais/uso terapêutico
Quimioterapia Combinada
Feminino
Seguimentos
Hepacivirus/efeitos dos fármacos
Hepatite C Crônica/virologia
Seres Humanos
Imidazóis/farmacologia
Imidazóis/uso terapêutico
Interferon-alfa/uso terapêutico
Isoquinolinas/farmacologia
Isoquinolinas/uso terapêutico
Masculino
Meia-Idade
Polietilenoglicóis/uso terapêutico
Inibidores de Proteases/farmacologia
Inibidores de Proteases/uso terapêutico
Proteínas Recombinantes/uso terapêutico
Ribavirina/farmacologia
Ribavirina/uso terapêutico
Simeprevir/farmacologia
Simeprevir/uso terapêutico
Sulfonamidas/farmacologia
Sulfonamidas/uso terapêutico
Fatores de Tempo
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (BMS-790052); 0 (Imidazoles); 0 (Interferon-alpha); 0 (Isoquinolines); 0 (NS-5 protein, hepatitis C virus); 0 (Protease Inhibitors); 0 (Recombinant Proteins); 0 (Sulfonamides); 0 (Viral Nonstructural Proteins); 30IQX730WE (Polyethylene Glycols); 49717AWG6K (Ribavirin); 9WS5RD66HZ (Simeprevir); EC 3.4.- (NS3-4A serine protease, Hepatitis C virus); EC 3.4.- (Serine Proteases); G8RGG88B68 (peginterferon alfa-2b); S9X0KRJ00S (asunaprevir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  6 / 22350 MEDLINE  
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[PMID]:27770745
[Au] Autor:Kocak A; Erol I; Yildiz M; Can H
[Ad] Endereço:Department of Chemistry, Gebze Technical University, 41400, Gebze, Kocaeli, Turkey. Electronic address: kocak@gtu.edu.tr.
[Ti] Título:Computational insights into the protonation states of catalytic dyad in BACE1-acyl guanidine based inhibitor complex.
[So] Source:J Mol Graph Model;70:226-235, 2016 11.
[Is] ISSN:1873-4243
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Developing small compound based drugs targeting the ß-secretase (BACE) enzyme is one of the most promising strategies in treatment of the Alzheimer's disease. As the enzyme shows the activity based on the acid-base reaction at a very narrow pH range, the protonation state of aspartic acids with the residue number 32 and 228 (Asp32 and Asp228), which forms the active site dyad, along with the protonation state of the ligand (substrate or inhibitor) play very critical role in interactions between the ligand and enzyme. Thus, understanding the nature of the protonation state of both enzyme's active site dyad and ligand is crucial for drug design in Alzheimer's disease field. Here we have investigated the protonation state of the Asp32 and Asp228 residues in the presence of a highly potent beta secretase inhibitor, containing acyl guanidine warhead that have recently been devised but not extensively studied. Our Quantum Mechanical, Molecular Dynamics and Docking studies on all the possible protonation states have suggested that the dyad residues are in di-deprotonated states in the presence of protonated inhibitor.
[Mh] Termos MeSH primário: Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores
Secretases da Proteína Precursora do Amiloide/química
Biocatálise
Guanidina/farmacologia
Modelos Moleculares
Inibidores de Proteases/química
Inibidores de Proteases/farmacologia
Prótons
[Mh] Termos MeSH secundário: Acilação
Guanidina/química
Ligações de Hidrogênio
Ligantes
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
Teoria Quântica
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Protease Inhibitors); 0 (Protons); EC 3.4.- (Amyloid Precursor Protein Secretases); JU58VJ6Y3B (Guanidine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


  7 / 22350 MEDLINE  
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[PMID]:27779422
[Au] Autor:Kouzaki H; Matsumoto K; Kikuoka H; Kato T; Tojima I; Shimizu S; Kita H; Shimizu T
[Ad] Endereço:1 Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Shiga, Japan; and.
[Ti] Título:Endogenous Protease Inhibitors in Airway Epithelial Cells Contribute to Eosinophilic Chronic Rhinosinusitis.
[So] Source:Am J Respir Crit Care Med;195(6):737-747, 2017 Mar 15.
[Is] ISSN:1535-4970
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Cystatin A and SPINK5 are endogenous protease inhibitors (EPIs) that may play key roles in epithelial barrier function. OBJECTIVES: To investigate the roles of EPIs in the pathogenesis of chronic rhinosinusitis (CRS). METHODS: We examined the expression of cystatin A and SPINK5 in the nasal epithelial cells of patients with CRS. Additionally, the in vitro effects of recombinant EPIs on the secretion of the epithelial-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin in airway epithelial cells, and the in vivo effects of recombinant EPIs in the nasal epithelium of mice exposed to multiple airborne allergens (MAA) were examined. MEASUREMENTS AND MAIN RESULTS: Compared with control subjects and patients with noneosinophilic CRS, patients with eosinophilic CRS showed significantly lower protein and mRNA expression of cystatin A and SPINK5 in the nasal epithelium. Allergen-induced production of IL-25, IL-33, and thymic stromal lymphopoietin in normal human bronchial epithelial cells was inhibited by treatment with recombinant cystatin A or SPINK5. Conversely, the production of these cytokines was increased when cystatin A or SPINK5 were knocked down with small interfering RNA. Chronic MAA exposure induced goblet cell metaplasia and epithelial disruption in mouse nasal epithelium and decreased the tissue expression and nasal lavage levels of cystatin A and SPINK5. Intranasal instillations of recombinant EPIs attenuated this MAA-induced pathology. CONCLUSIONS: Cystatin A and SPINK5 play an important role in protecting the airway epithelium from exogenous proteases. The preservation of EPIs may have a therapeutic benefit in intractable airway inflammation, such as eosinophilic CRS.
[Mh] Termos MeSH primário: Eosinofilia/metabolismo
Células Epiteliais/metabolismo
Inibidores de Proteases/metabolismo
Rinite/metabolismo
Sinusite/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Animais
Doença Crônica
Cistatina A/metabolismo
Eosinofilia/complicações
Feminino
Seres Humanos
Interleucina-17/metabolismo
Interleucina-33/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Meia-Idade
Mucosa Nasal/metabolismo
Proteínas Secretadas Inibidoras de Proteinases/metabolismo
Rinite/complicações
Inibidor de Serinopeptidase do Tipo Kazal 5
Sinusite/complicações
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cystatin A); 0 (Interleukin-17); 0 (Interleukin-33); 0 (Protease Inhibitors); 0 (Proteinase Inhibitory Proteins, Secretory); 0 (SPINK5 protein, human); 0 (Serine Peptidase Inhibitor Kazal-Type 5)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1164/rccm.201603-0529OC


  8 / 22350 MEDLINE  
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[PMID]:29236775
[Au] Autor:Wang F; Wang L; Wu J; Sokirniy I; Nguyen P; Bregnard T; Weinstock J; Mattern M; Bezsonova I; Hancock WW; Kumar S
[Ad] Endereço:Progenra Inc, Malvern, Pennsylvania, United States of America.
[Ti] Título:Active site-targeted covalent irreversible inhibitors of USP7 impair the functions of Foxp3+ T-regulatory cells by promoting ubiquitination of Tip60.
[So] Source:PLoS One;12(12):e0189744, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Accumulation of Foxp3+ T-regulatory (Treg) cells in the tumor microenvironment is associated with tumor immune evasion and poor patient outcome in the case of many solid tumors. Current therapeutic strategies for blocking Treg functions are not Treg-specific, and display only modest and transient efficacy. Recent studies revealed that ubiquitin-specific protease 7 (USP7) is essential for Treg functions by stabilizing expression of Tip60 and Foxp3, which together are central to the development and maintenance of the Treg cell lineage. Pharmacological inhibition of USP7 is therefore a promising strategy for suppressing Treg functions and promoting anti-tumor immunity. Previously, we reported the P5091 series of small molecule USP7 inhibitors and demonstrated their direct anti-tumor activity in vivo using xenograft models. However, the precise mechanism of action of these compounds was not well defined. In this study, we report the development and characterization of P217564, a second-generation USP7 inhibitor with improved potency and selectivity. P217564 selectively targets the catalytic cleft of USP7 and modifies its active site cysteine (C223) by forming a covalent adduct. Irreversible inhibition of USP7 results in durable downstream biological responses in cells, including down-regulation of Tip60 and consequent impairment of Treg suppressive function. In addition, we demonstrate that both USP7 and various USP7 substrates are subjected to Lys48-mediated ubiquitin modification, consistent with increased proteasomal degradation of these proteins because of USP7 inhibition.
[Mh] Termos MeSH primário: Proteínas de Drosophila/metabolismo
Fatores de Transcrição Forkhead/metabolismo
Histona Acetiltransferases/metabolismo
Linfócitos T Reguladores/imunologia
Peptidase 7 Específica de Ubiquitina/antagonistas & inibidores
[Mh] Termos MeSH secundário: Domínio Catalítico
Linhagem Celular Tumoral
Seres Humanos
Inibidores de Proteases/farmacologia
Peptidase 7 Específica de Ubiquitina/metabolismo
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors); 0 (Protease Inhibitors); EC 2.3.1.48 (Histone Acetyltransferases); EC 2.3.1.48 (Tip60 protein, Drosophila); EC 3.4.19.12 (USP7 protein, human); EC 3.4.19.12 (Ubiquitin-Specific Peptidase 7)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189744


  9 / 22350 MEDLINE  
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[PMID]:28456986
[Au] Autor:Rawlings ND
[Ad] Endereço:European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. ndr@ebi.ac.uk.
[Ti] Título:Using the MEROPS Database for Investigation of Lysosomal Peptidases, Their Inhibitors, and Substrates.
[So] Source:Methods Mol Biol;1594:213-226, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This chapter describes how to retrieve data on lysosomal peptidases from the MEROPS database for proteolytic enzymes, their substrates and inhibitors ( http://merops.sanger.ac.uk ). Features described in this chapter include the summary page, pages for structure, interactions with inhibitors, substrates, literature and involvement in physiological pathways, and how to download data from the MEROPS FTP site. The lysosomal peptidase legumain is used as an example.
[Mh] Termos MeSH primário: Bases de Dados de Proteínas
Peptídeo Hidrolases/análise
Proteínas/análise
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Inibidores de Proteases
Proteínas/antagonistas & inibidores
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protease Inhibitors); 0 (Proteins); 0 (lysosomal proteins); EC 3.4.- (Peptide Hydrolases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6934-0_14


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[PMID]:29320547
[Au] Autor:Augustemak de Lima LR; Petroski EL; Moreno YMF; Silva DAS; Trindade EBMS; Carvalho AP; Back IC
[Ad] Endereço:Research Centre for Kinanthropometry and Human Performance. Department of Physical Education. Federal University of Santa Catarina. Florianópolis, Santa Catarina, Brazil.
[Ti] Título:Dyslipidemia, chronic inflammation, and subclinical atherosclerosis in children and adolescents infected with HIV: The PositHIVe Health Study.
[So] Source:PLoS One;13(1):e0190785, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HIV-infected children and adolescents may be at risk for cardiovascular disease due to chronic inflammation and exacerbation of risk factors. The aim of this study was as follows: 1) compare cardiovascular risk factors, chronic inflammation, and carotid intima-media thickness (IMTc) between the HIV and control groups; 2) determine the association of HIV and antiretroviral (ART) regimens with cardiovascular risk factors, chronic inflammation, and IMTc; and 3) identify variables associated with elevated IMTc. Cross-sectional analysis of 130 children and adolescents, 8-15 years of age, divided into HIV-infected (n = 65) and healthy control (n = 65) participants. Body fat, blood pressure, glycemia, insulin, and glycated hemoglobin, total cholesterol and fractions (LDL-C and HDL-C), triglycerides, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and the IMTc were measured. The results showed HIV-infected children and adolescents had higher levels of glycemia (87.9 vs. 75.9 mg.dL-1, p< 0.001), LDL-c (94.7 vs. 79.5 mg.dL-1, p = 0.010), triglycerides (101.2 vs. 61.6 mg.dL-1, p< 0.001), CRP (1.6 vs. 1.0 mg.L-1, p = 0.007), IL-6 (1.42 vs. 0.01 pg.mL-1, p< 0.001), TNF-α (0.49 vs. 0.01 pg.mL-1, p< 0.001), mean IMTc (0.526 vs. 0.499 mm, p = 0.009), and lower HDL-c (53.7 vs. 69.4 mg.dL-1, p< 0.001) compared to controls. Systolic blood pressure (ß = 0.006, p = 0.004) and TNF-α (ß = -0.033, p = 0.029) accounted for 16% of IMTc variability in HIV-infected children and adolescents. In patients using protease inhibitors-based ART, male gender (ß = -0.186, p = 0.008), trunk body fat (ß = -0.011, p = 0.006), glucose (ß = 0.005, p = 0.046), and IL-6 (ß = 0.017, p = 0.039) accounted for 28% of IMTc variability. HIV-infected children and adolescents may be at risk for premature atherosclerosis due to chronic inflammation and dyslipidemia. Interventions with the potential to improve lipid profile, mitigate inflammation, and reduce cardiovascular risk are needed.
[Mh] Termos MeSH primário: Aterosclerose/complicações
Dislipidemias/complicações
Infecções por HIV/complicações
Inflamação/complicações
[Mh] Termos MeSH secundário: Adiposidade
Adolescente
Antirretrovirais/uso terapêutico
Aterosclerose/diagnóstico por imagem
Aterosclerose/epidemiologia
Aterosclerose/fisiopatologia
Biomarcadores/sangue
Glicemia
Espessura Intima-Media Carotídea
Criança
Estudos Transversais
Dislipidemias/diagnóstico por imagem
Dislipidemias/epidemiologia
Dislipidemias/fisiopatologia
Feminino
Infecções por HIV/diagnóstico por imagem
Infecções por HIV/tratamento farmacológico
Infecções por HIV/fisiopatologia
Seres Humanos
Inflamação/diagnóstico por imagem
Inflamação/epidemiologia
Inflamação/fisiopatologia
Interleucina-6/sangue
Lipídeos/sangue
Masculino
Inibidores de Proteases/uso terapêutico
Fatores de Risco
Fatores Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); 0 (Biomarkers); 0 (Blood Glucose); 0 (IL6 protein, human); 0 (Interleukin-6); 0 (Lipids); 0 (Protease Inhibitors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190785



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