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  1 / 1915 MEDLINE  
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[PMID]:28465627
[Au] Autor:Falzone M; Crespo E; Jones K; Khan G; Korn VL; Patel A; Patel M; Patel K; Perkins C; Siddiqui S; Stenger D; Yu E; Gelber M; Scheffler R; Nayda V; Ravin A; Komal R; Rudolf JD; Shen B; Gullo V; Demain AL
[Ad] Endereço:Research Institute of Scientists Emeriti (RISE), Charles A. Dana Research Institute, Drew University, Madison, NJ, USA.
[Ti] Título:Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of l-aspartic acid.
[So] Source:J Antibiot (Tokyo);70(7):828-831, 2017 Jul.
[Is] ISSN:0021-8820
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Streptomyces platensis MA7327 is a bacterium producing interesting antibiotics, which act by the novel mechanism of inhibiting fatty acid biosynthesis. The antibiotics produced by this actinomycete are platensimycin and platencin plus some minor related antibiotics. Platensimycin and platencin have activity against antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus; they also lack toxicity in animal models. Platensimycin also has activity against diabetes in a mouse model. We have been interested in studying the effects of primary metabolites on production of these antibiotics in our chemically defined production medium. In the present work, we tested 32 primary metabolites for their effect. They included 20 amino acids, 7 vitamins and 5 nucleic acid derivatives. Of these, only l-aspartic acid showed stimulation of antibiotic production. We conclude that the stimulatory effect of aspartic acid is due to its role as a precursor involved in the biosynthesis of aspartate-4-semialdehyde, which is the starting point for the biosynthesis of the 3-amino-2,4-dihydroxy benzoic acid portion of the platensimycin molecule.
[Mh] Termos MeSH primário: Antibacterianos/isolamento & purificação
Ácido Aspártico/administração & dosagem
Streptomyces/metabolismo
[Mh] Termos MeSH secundário: Adamantano/isolamento & purificação
Aminoácidos/administração & dosagem
Aminoácidos/metabolismo
Aminobenzoatos/isolamento & purificação
Aminofenóis/isolamento & purificação
Anilidas/isolamento & purificação
Antibacterianos/biossíntese
Ácido Aspártico/química
Ácidos Nucleicos/administração & dosagem
Ácidos Nucleicos/metabolismo
Compostos Policíclicos/isolamento & purificação
Vitaminas/administração & dosagem
Vitaminas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Aminobenzoates); 0 (Aminophenols); 0 (Anilides); 0 (Anti-Bacterial Agents); 0 (Nucleic Acids); 0 (Polycyclic Compounds); 0 (Vitamins); 0 (platencin); 30KYC7MIAI (Aspartic Acid); PJY633525U (Adamantane); Q3DQ78KOFY (platensimycin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1038/ja.2017.49


  2 / 1915 MEDLINE  
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[PMID]:27776232
[Au] Autor:Ferreira CIA; Calisto V; Otero M; Nadais H; Esteves VI
[Ad] Endereço:Department of Chemistry and CESAM (Centre for Environmental and Marine Studies), University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal.
[Ti] Título:Removal of tricaine methanesulfonate from aquaculture wastewater by adsorption onto pyrolysed paper mill sludge.
[So] Source:Chemosphere;168:139-146, 2017 Feb.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Tricaine methanesulfonate (MS-222) has been widely used in intensive aquaculture systems to control stress during handling and confinement operations. This compound is dissolved in the water tanks and, once it is present in the Recirculating Aquaculture Systems (RASs), MS-222 can reach the environment by the discharge of contaminated effluents. The present work proposes the implementation of the adsorption process in the RASs, using pyrolysed biological paper mill sludge as adsorbent, to remove MS-222 from aquaculture wastewater. Adsorption experiments were performed under extreme operating conditions, simulating those corresponding to different farmed fish species: temperature (from 8 to 30 °C), salinity (from 0.8 to 35‰) and different contents of organic and inorganic matter in the aquaculture wastewater. Furthermore, the MS-222 adsorption from a real aquaculture effluent was compared with that from ultrapure water. Under the studied conditions, the performance of the produced adsorbent remained mostly the same, removing satisfactorily MS-222 from water. Therefore, it may be concluded that the produced adsorbent can be employed in intensive aquaculture wastewater treatment with the same performance independently of the farmed fish species.
[Mh] Termos MeSH primário: Aminobenzoatos/análise
Aquicultura
Esgotos/química
Águas Residuais/química
Poluentes Químicos da Água/análise
Purificação da Água/métodos
[Mh] Termos MeSH secundário: Adsorção
Resíduos Industriais
Papel
Temperatura Ambiente
Eliminação de Resíduos Líquidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (Industrial Waste); 0 (Sewage); 0 (Waste Water); 0 (Water Pollutants, Chemical); 02591PHL19 (tricaine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171212
[Lr] Data última revisão:
171212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  3 / 1915 MEDLINE  
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[PMID]:28927529
[Au] Autor:Berardinelli F; Coluzzi E; Sgura A; Antoccia A
[Ad] Endereço:Dipartimento di Scienze, Università Roma Tre, Rome Italy; Istituto Nazionale di Fisica Nucleare, INFN, Sezione di Roma Tre, Rome, Italy. Electronic address: francesco.berardinelli@uniroma3.it.
[Ti] Título:Targeting telomerase and telomeres to enhance ionizing radiation effects in in vitro and in vivo cancer models.
[So] Source:Mutat Res;773:204-219, 2017 Jul.
[Is] ISSN:1873-135X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:One of the hallmarks of cancer consists in the ability of tumor cells to divide indefinitely, and to maintain stable telomere lengths throughout the activation of specific telomere maintenance mechanisms (TMM). Therefore in the last fifteen years, researchers proposed to target telomerase or telomeric structure in order to block limitless replicative potential of cancer cells providing a fascinating strategy for a broad-spectrum cancer therapy. In the present review, we report in vitro and in vivo evidence regarding the use of chemical agents targeting both telomerase or telomere structure and showing promising antitumor effects when used in combination with ionizing radiation (IR). RNA interference, antisense oligonucleotides (e.g., GRN163L), non-nucleoside inhibitors (e.g., BIBR1532) and nucleoside analogs (e.g., AZT) represent some of the most potent strategies to inhibit telomerase activity used in combination with IR. Furthermore, radiosensitizing effects were demonstrated also for agents acting directly on the telomeric structure such as G4-ligands (e.g., RHPS4 and Telomestatin) or telomeric-oligos (T-oligos). To date, some of these compounds are under clinical evaluation (e.g., GRN163L and KML001). Advantages of Telomere/Telomerase Targeting Compounds (T/TTCs) coupled with radiotherapy may be relevant in the treatment of radioresistant tumors and in the development of new optimized treatment plans with reduced dose adsorbed by patients and consequent attenuation of short- end long-term side effects. Pros and cons of possible future applications in cancer therapy based on the combination of T/TCCs and radiation treatment are discussed.
[Mh] Termos MeSH primário: Neoplasias/tratamento farmacológico
Neoplasias/radioterapia
Radiação Ionizante
Telomerase/metabolismo
Telômero/metabolismo
[Mh] Termos MeSH secundário: Aminobenzoatos/farmacologia
Animais
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/efeitos da radiação
Modelos Animais de Doenças
Homeostase/efeitos dos fármacos
Homeostase/efeitos da radiação
Seres Humanos
Naftalenos/farmacologia
Oligonucleotídeos/farmacologia
Interferência de RNA
Radiossensibilizantes/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (BIBR 1532); 0 (GRN163L peptide); 0 (Naphthalenes); 0 (Oligonucleotides); 0 (Radiation-Sensitizing Agents); EC 2.7.7.49 (Telomerase)
[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:170921
[St] Status:MEDLINE


  4 / 1915 MEDLINE  
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[PMID]:28678815
[Au] Autor:Skår MW; Haugland GT; Powell MD; Wergeland HI; Samuelsen OB
[Ad] Endereço:Department of Biology, University of Bergen, Bergen, Norway.
[Ti] Título:Development of anaesthetic protocols for lumpfish (Cyclopterus lumpus L.): Effect of anaesthetic concentrations, sea water temperature and body weight.
[So] Source:PLoS One;12(7):e0179344, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In recent years, use of lumpfish (Cyclopterus lumpus L.) as cleaner-fish to remove sea-lice have been chosen by many salmon farmers in Europe and Canada as an alternative to medical treatment, which has led to large scale production of lumpfish. At present, there is limited knowledge of how lumpfish respond upon anaesthesia, which anaesthetics and concentrations that are efficient and conditions for euthanasia. We have therefore tested and developed protocols for bath immersion for three commonly used anaesthetics metacaine (Finquel, buffered tricaine methanesulfonate, MS-222 and Tricaine Pharmaq), benzocaine (Benzoak vet) and isoeugenol (Aqui-S), determined concentration for normal and fast anaesthesia and evaluated safety margin for each condition. Also, a behavioral matrix has been developed. We have examined the effect of fish size (10-20 g, 200-400 g and 600-1300 g) and sea water temperature (6°C and 12°C). We found that 200 mg L-1 metacaine is an efficient dose for deep narcosis independently for fish size and temperature due to good safety margins with regards to both exposure times and doses. However, for many tasks lighter anaesthesia is sufficient, and then 100 mg L-1 metacaine can be used. Benzocaine is less efficient than metacaine, but can be used as anaesthetic of fish < 400 g. The optimal doses of benzocaine were 100-200 mg L-1 for small fish (10-20 g) and 200 mg L-1 for medium sized fish (200-400 g). For larger fish (> 600 g), benzocaine is not suitable. Isoeugenol cannot be recommended for full anesthesia of lumpfish. The conditions for lethal doses varied with chosen anaesthetic, fish size and temperature. For small fish (10-20 g), exposure to 1600 mgL-1 of metacaine in 10 minutes it lethal. Guided protocols for non-lethal anaesthesia will contribute to ensure safe treatment of lumpfish according to an ethical standard for good fish welfare.
[Mh] Termos MeSH primário: Anestesia/métodos
Anestésicos/farmacologia
Comportamento Animal/efeitos dos fármacos
Perciformes/fisiologia
[Mh] Termos MeSH secundário: Aminobenzoatos/administração & dosagem
Aminobenzoatos/farmacologia
Anestésicos/administração & dosagem
Bem-Estar do Animal/normas
Animais
Benzocaína/administração & dosagem
Benzocaína/farmacologia
Peso Corporal
Relação Dose-Resposta a Droga
Eugenol/administração & dosagem
Eugenol/análogos & derivados
Eugenol/farmacologia
Recuperação de Função Fisiológica
Reprodutibilidade dos Testes
Respiração
Água do Mar/química
Natação
Temperatura Ambiente
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (Anesthetics); 02591PHL19 (tricaine); 3T8H1794QW (Eugenol); 5M0MWY797U (isoeugenol); U3RSY48JW5 (Benzocaine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170706
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179344


  5 / 1915 MEDLINE  
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[PMID]:28662334
[Au] Autor:Dal Corso A; Cazzamalli S; Gébleux R; Mattarella M; Neri D
[Ad] Endereço:Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich) , Vladimir-Prelog-Weg 4, CH-8093 Zürich, Switzerland.
[Ti] Título:Protease-Cleavable Linkers Modulate the Anticancer Activity of Noninternalizing Antibody-Drug Conjugates.
[So] Source:Bioconjug Chem;28(7):1826-1833, 2017 Jul 19.
[Is] ISSN:1520-4812
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Antibody-drug conjugates (ADCs) represent an attractive class of biopharmaceutical agents, with the potential to selectively deliver potent cytotoxic agents to tumors. It is generally assumed that ADC products should preferably bind and internalize into cancer cells in order to liberate their toxic payload, but a growing body of evidence indicates that also ADCs based on noninternalizing antibodies may be potently active. In this Communication, we investigated dipeptide-based linkers (frequently used for internalizing ADC products) in the context of the noninternalizing F16 antibody, specific to a splice isoform of tenascin-C. Using monomethyl auristatin E (MMAE) as potent cytotoxic drug, we observed that a single amino acid substitution of the Val-Cit dipeptide linker can substantially modulate the in vivo stability of the corresponding ADC products, as well as the anticancer activity in mice bearing the human epidermoid A431 carcinoma. In these settings, the linker based on the Val-Ala dipeptide exhibited better performances, compared to Val-Cit, Val-Lys, and Val-Arg analogues. Mass spectrometric analysis revealed that the four linkers displayed not only different stability in vivo but also differences in cleavage sites. Moreover, the absence of anticancer activity for a F16-MMAE conjugate featuring a noncleavable linker indicated that drug release modalities, based on proteolytic degradation of the immunoglobulin moiety, cannot be exploited with noninternalizing antibodies. ADC products based on the noninternalizing F16 antibody may be useful for the treatment of several human malignancies, as the cognate antigen is abundantly expressed in the extracellular matrix of several tumors, while being virtually undetectable in most normal adult tissues.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Dipeptídeos/metabolismo
Imunoconjugados/química
Peptídeo Hidrolases/metabolismo
[Mh] Termos MeSH secundário: Alanina
Aminobenzoatos/administração & dosagem
Aminobenzoatos/química
Animais
Antineoplásicos/administração & dosagem
Antineoplásicos/química
Matriz Extracelular/química
Matriz Extracelular/imunologia
Seres Humanos
Imunoconjugados/metabolismo
Camundongos
Oligopeptídeos/administração & dosagem
Oligopeptídeos/química
Tenascina/genética
Tenascina/imunologia
Valina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (Antineoplastic Agents); 0 (Dipeptides); 0 (Immunoconjugates); 0 (Oligopeptides); 0 (Tenascin); 0 (auristatin); EC 3.4.- (Peptide Hydrolases); HG18B9YRS7 (Valine); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1021/acs.bioconjchem.7b00304


  6 / 1915 MEDLINE  
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[PMID]:28590752
[Au] Autor:Grünewald J; Jin Y; Vance J; Read J; Wang X; Wan Y; Zhou H; Ou W; Klock HE; Peters EC; Uno T; Brock A; Geierstanger BH
[Ad] Endereço:Genomics Institute of the Novartis Research Foundation (GNF) , 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
[Ti] Título:Optimization of an Enzymatic Antibody-Drug Conjugation Approach Based on Coenzyme A Analogs.
[So] Source:Bioconjug Chem;28(7):1906-1915, 2017 Jul 19.
[Is] ISSN:1520-4812
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phosphopantetheine transferases (PPTases) can be used to efficiently prepare site-specific antibody-drug conjugates (ADCs) by enzymatically coupling coenzyme A (CoA)-linker payloads to 11-12 amino acid peptide substrates inserted into antibodies. Here, a two-step strategy is established wherein in a first step, CoA analogs with various bioorthogonal reactivities are enzymatically installed on the antibody for chemical conjugation with a cytotoxic payload in a second step. Because of the high structural similarity of these CoA analogs to the natural PPTase substrate CoA-SH, the first step proceeds very efficiently and enables the use of peptide tags as short as 6 amino acids compared to the 11-12 amino acids required for efficient one-step coupling of the payload molecule. Furthermore, two-step conjugation provides access to diverse linker chemistries and spacers of varying lengths. The potency of the ADCs was largely independent of linker architecture. In mice, proteolytic cleavage was observed for some C-terminally linked auristatin payloads. The in vivo stability of these ADCs was significantly improved by reduction of the linker length. In addition, linker stability was found to be modulated by attachment site, and this, together with linker length, provides an opportunity for maximizing ADC stability without sacrificing potency.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/química
Coenzima A/química
Citotoxinas/química
Imunoconjugados/química
[Mh] Termos MeSH secundário: Aminobenzoatos/administração & dosagem
Aminobenzoatos/química
Animais
Citotoxinas/administração & dosagem
Estabilidade de Medicamentos
Camundongos
Oligopeptídeos/administração & dosagem
Oligopeptídeos/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (Antibodies, Monoclonal); 0 (Cytotoxins); 0 (Immunoconjugates); 0 (Oligopeptides); 0 (auristatin); SAA04E81UX (Coenzyme A)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE
[do] DOI:10.1021/acs.bioconjchem.7b00236


  7 / 1915 MEDLINE  
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[PMID]:28504888
[Au] Autor:Chen L; Chai W; Wang W; Song T; Lian XY; Zhang Z
[Ad] Endereço:Ocean College, Zhoushan Campus, Zhejiang University , Zhoushan 316021, People's Republic of China.
[Ti] Título:Cytotoxic Bagremycins from Mangrove-Derived Streptomyces sp. Q22.
[So] Source:J Nat Prod;80(5):1450-1456, 2017 May 26.
[Is] ISSN:1520-6025
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:New bagremycins C-E (3-5) and bagrelactone A (6), together with known bagremycins A (1) and B (2), 4-hydroxystyrene (7), and 4-hydroxystyrene 4-O-α-d-galactopyranoside (8), were isolated from a mangrove-derived actinomycete, Streptomyces sp. Q22. Structures of these new compounds were elucidated based on their NMR and HRESIMS spectroscopic data as well as chemical degradation. Bagremycin C (3) is a unique analogue with an N-acetyl-(S)-cysteine moiety, while bagrelactone A (6) represents the first example of this type of bagremycin-derived macrolide. Bagremycin C (3) was active against four glioma cell lines, with IC values in the range from 2.2 to 6.4 µM, induced apoptosis in human glioma U87MG cells in a dose- and time-dependent manner, and arrested the U87MG cell cycle at the G /G phase.
[Mh] Termos MeSH primário: Actinobacteria/química
Aminobenzoatos/farmacologia
Antibacterianos/farmacologia
Antineoplásicos/farmacologia
Glioma/tratamento farmacológico
Macrolídeos/farmacologia
Fenóis/química
Streptomyces/química
[Mh] Termos MeSH secundário: Aminobenzoatos/química
Antibacterianos/química
Antineoplásicos/química
Linhagem Celular Tumoral
Ensaios de Seleção de Medicamentos Antitumorais
Glioma/química
Seres Humanos
Concentração Inibidora 50
Macrolídeos/química
Estrutura Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (Anti-Bacterial Agents); 0 (Antineoplastic Agents); 0 (Macrolides); 0 (Phenols); 0 (bagremycin A); 0 (bagremycin B); 0 (bagremycin C); OA7V1SM8YL (4-vinylphenol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jnatprod.6b01136


  8 / 1915 MEDLINE  
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[PMID]:28432000
[Au] Autor:Furuki K; Toyo'oka T
[Ad] Endereço:Process Science Lab II, Biotechnology Labs, Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba-shi, Ibaraki 300-2698, Japan; School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan. Electronic address: kenfuruki@yahoo.co.jp.
[Ti] Título:Determination of thiol-to-protein ratio and drug-to-antibody ratio by in-line size exclusion chromatography with post-column reaction.
[So] Source:Anal Biochem;527:33-44, 2017 Jun 15.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:An in-line size-exclusion (SE) ultra-high-performance liquid chromatography (UHPLC)- 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) method to quantify thiols in monoclonal antibodies (mAb) when manufacturing antibody-drug conjugates (ADCs) was developed. The mAbs are separated on an SE-UHPLC column and monitored with a UV detector at a wavelength of 280 nm. Eluents are channeled into a reaction coil and mixed with DTNB to form 5-thio-2-nitrobenzoic acid (TNB). Thiol concentration is calculated using absorption at 412 nm. Using optimized conditions, partially reduced mAbs can be separated from low-molecular weight contaminants and undergo the DTNB reaction. The standard curve of L-cysteine had good linearity between 100 and 1000 µM. The selectivity, linearity, repeatability, and robustness of this method were evaluated. The calculated free-SH:protein ratios of partially reduced mAbs were consistent between in-line SE-UHPLC-DTNB and conventional methods. The SE-UHPLC-DTNB method showed time- and temperature-dependent changes in the free-SH:protein ratio of mAbs during reduction. The changes in drug-antibody ratio (DAR) of ADCs during the conjugation reaction were also evaluated. This method is an inexpensive and versatile alternative to conventional methods of estimating the free-SH:protein ratio of mAbs and the DAR of ADCs. This method also minimizes assay time.
[Mh] Termos MeSH primário: Aminobenzoatos/análise
Anticorpos Monoclonais/análise
Cromatografia em Gel/métodos
Ácido Ditionitrobenzoico/química
Imunoconjugados/análise
Oligopeptídeos/análise
Compostos de Sulfidrila/análise
[Mh] Termos MeSH secundário: Aminobenzoatos/química
Anticorpos Monoclonais/química
Calibragem
Cromatografia Líquida de Alta Pressão
Cisteína/análise
Seres Humanos
Imunoconjugados/química
Imunoglobulina G/análise
Imunoglobulina G/química
Cinética
Oligopeptídeos/química
Oxirredução
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Compostos de Sulfidrila/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (Antibodies, Monoclonal); 0 (Immunoconjugates); 0 (Immunoglobulin G); 0 (Oligopeptides); 0 (Sulfhydryl Compounds); 0 (auristatin); 9BZQ3U62JX (Dithionitrobenzoic Acid); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170526
[Lr] Data última revisão:
170526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170423
[St] Status:MEDLINE


  9 / 1915 MEDLINE  
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[PMID]:28361465
[Au] Autor:Lambert JM; Morris CQ
[Ad] Endereço:ImmunoGen, Inc., Waltham, MA, USA. John.Lambert@immunogen.com.
[Ti] Título:Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review.
[So] Source:Adv Ther;34(5):1015-1035, 2017 May.
[Is] ISSN:1865-8652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial. The development of two classes of highly potent microtubule-disrupting agents, maytansinoids and auristatins, as payloads for ADCs resulted in approval of brentuximab vedotin in 2011 for treating Hodgkin lymphoma and anaplastic large cell lymphoma, and approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive breast cancer. Their success stimulated much research into the ADC approach, with >60 ADCs currently in clinical evaluation, mostly targeting solid tumors. Five ADCs have advanced into pivotal clinical trials for treating various solid tumors-platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, and small cell lung cancer. The level of target expression is a key parameter in predicting the likelihood of patient benefit for all these ADCs, as well as for the approved compound, ado-trastuzumab emtansine. The development of a patient selection strategy linked to target expression on the tumor is thus critically important for identifying the population appropriate for receiving treatment.
[Mh] Termos MeSH primário: Aminobenzoatos/uso terapêutico
Aminoglicosídeos/uso terapêutico
Anticorpos Monoclonais Humanizados/uso terapêutico
Antineoplásicos/uso terapêutico
Imunoconjugados/uso terapêutico
Maitansina/análogos & derivados
Neoplasias/tratamento farmacológico
Oligopeptídeos/uso terapêutico
Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/uso terapêutico
[Mh] Termos MeSH secundário: Seres Humanos
Maitansina/uso terapêutico
Neoplasias/imunologia
Trastuzumab
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (Aminoglycosides); 0 (Antibodies, Monoclonal, Humanized); 0 (Antineoplastic Agents); 0 (Immunoconjugates); 0 (Oligopeptides); 0 (Sialic Acid Binding Ig-like Lectin 3); 0 (auristatin); 14083FR882 (Maytansine); 93NS566KF7 (gemtuzumab); P188ANX8CK (Trastuzumab); SE2KH7T06F (ado-trastuzumab emtansine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:T
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.1007/s12325-017-0519-6


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[PMID]:28237556
[Au] Autor:Dong LB; Rudolf JD; Lin L; Ruiz C; Cameron MD; Shen B
[Ad] Endereço:Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, United States.
[Ti] Título:In vivo instability of platensimycin and platencin: Synthesis and biological evaluation of urea- and carbamate-platensimycin.
[So] Source:Bioorg Med Chem;25(6):1990-1996, 2017 Mar 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Platensimycin (PTM) and platencin (PTN), two natural products and promising drug leads that target bacterial and mammalian fatty acid synthases, are known to have unfavorable pharmacokinetic properties. It is not clear, however, what the metabolic fates of PTM and PTN are and no efforts have been reported to address this key roadblock in the development of these compounds as viable drug options. Here we describe the pharmacokinetics of PTM and PTN, and reveal rapid renal clearance as the primary metabolic liability with three additional sites of chemical liability: (i) amide hydrolysis, (ii) glucuronidation, and (iii) oxidation. We determined that hydrolysis is a viable clearance mechanism in vivo and synthesized two PTM analogues to address in vivo hydrolysis. Urea- and carbamate-PTM analogues showed no detectable hydrolysis in vivo, at the expense of antibacterial activity, with no further improvement in systemic exposure. The antibacterial sulfur-containing analogues PTM D1 and PTM ML14 showed significant decreases in renal clearance. These studies set the stage for continued generation of PTM and PTN analogues in an effort to improve their pharmacokinetics while retaining or improving their biological activities.
[Mh] Termos MeSH primário: Adamantano/síntese química
Adamantano/farmacologia
Aminobenzoatos/síntese química
Aminobenzoatos/farmacologia
Aminofenóis/síntese química
Aminofenóis/farmacologia
Anilidas/síntese química
Anilidas/farmacologia
Antibacterianos/síntese química
Antibacterianos/farmacologia
Carbamatos/química
Compostos Policíclicos/síntese química
Compostos Policíclicos/farmacologia
Ureia/química
[Mh] Termos MeSH secundário: Animais
Espectroscopia de Ressonância Magnética Nuclear de Carbono-13
Camundongos
Camundongos Endogâmicos C57BL
Espectroscopia de Prótons por Ressonância Magnética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (Aminophenols); 0 (Anilides); 0 (Anti-Bacterial Agents); 0 (Carbamates); 0 (Polycyclic Compounds); 0 (platencin); 8W8T17847W (Urea); PJY633525U (Adamantane); Q3DQ78KOFY (platensimycin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170227
[St] Status:MEDLINE



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