Protein Kinases as Drug Targets in Human and Animal Diseases

2017 ◽  
Vol 13 (2) ◽  
Author(s):  
Suvarna G. Kini ◽  
Vikas Garg ◽  
Sharada Prasanna ◽  
Revathi Rajappan ◽  
Muhammad Mubeen
2021 ◽  
Author(s):  
Zhengyan Guo ◽  
Yue Tang ◽  
Wei Tang ◽  
Yihua Chen

Heptose-containing natural products hold great potential as drugs for the treatment of human and animal diseases.


Insects ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 366
Author(s):  
Raisa Rodrigues Santos Rios ◽  
Maria Clara Alves Santarém ◽  
Karlos Antônio Lisboa Ribeiro Júnior ◽  
Breno Araujo de Melo ◽  
Sybelle Georgia Mesquita da Silva ◽  
...  

The species of the Culicoides genus are hematophagous, and some of them are vectors of important human and animal diseases. This group of insects is distributed worldwide, varying according to local species. Knowledge of the geographic distribution of specific species is crucial for the development and implementation of control strategies. The aim of this work was to investigate the occurrence of Culicoides in the state of Alagoas in northeast Brazil. Midges were captured with CDC light traps, and their identification and morphological analyses were performed by the Ceratopogonidae Collection of the Oswaldo Cruz Foundation (FIOCRUZ/CCER) in Rio de Janeiro, Brazil. Morphological analyses were performed using the key to Culicoides from the guttatus group and comparison with other deposited specimens. DNA sequencing, genetic analysis and comparison with sequences in the Genbank database, confirmed the identification of the flies as Culicoides insignis. This was the first formal report of C. insignis being found in Alagoas.


10.2741/4862 ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1412-1432 ◽  
Author(s):  
Saif Hameed
Keyword(s):  

2016 ◽  
Author(s):  
Zheng Zhao ◽  
Lei Xie ◽  
Philip E. Bourne

AbstractProtein kinases are critical drug targets for treating a large variety of human diseases. Type-I and type-II kinase inhibitors frequently exhibit off-target toxicity or lead to mutation acquired resistance. Two highly specific allosteric type-III MEK-targeted drugs, Trametinib and Cobimetinib, offer a new approach. Thus, understanding the binding mechanism of existing type-III kinase inhibitors will provide insights for designing new type-III kinase inhibitors. In this work we have systematically studied the binding mode of MEK-targeted type-III inhibitors using structural systems pharmacology and molecular dynamics simulation. Our studies provide detailed sequence, structure, interaction-fingerprint, pharmacophore and binding-site information on the binding characteristics of MEK type-III kinase inhibitors. We propose that the helix-folding activation loop is a hallmark allosteric binding site for type-III inhibitors. Subsequently we screened and predicted allosteric binding sites across the human kinome, suggesting other kinases as potential targets suitable for type-III inhibitors. Our findings will provide new insights into the design of potent and selective kinases inhibitors.Author SummaryHuman protein kinases represent a large protein family relevant to many diseases, especially cancers, and have become important drug targets. However, developing the desired selective kinase-targeted inhibitors remain challenging. Kinase allosteric inhibitors provide that opportunity, but, to date, few have been designed other than MEK inhibitors. To more efficiently develop kinase allosteric inhibitors, we systematically studied the binding mode of the MEK type-III allosteric kinase inhibitors using structural system pharmacology and molecular dynamics approaches. New insights into the binding mode and mechanism of type-III inhibitors were revealed that may facilitate the design of new prospective type-III kinase inhibitors.


2014 ◽  
Vol 63 (5) ◽  
pp. 659-666 ◽  
Author(s):  
Kazumasa Kamei ◽  
Masahiro Asakura ◽  
Srinuan Somroop ◽  
Noritoshi Hatanaka ◽  
Atsushi Hinenoya ◽  
...  

Although Campylobacter jejuni and Campylobacter coli are the most common bacterial causes of human gastrointestinal diseases, other Campylobacter species are also involved in human and animal infections. In this study, we developed a cytolethal distending toxin (cdt) gene-based PCR-RFLP assay for the detection and differentiation of C. jejuni, C. coli, C. fetus, C. hyointestinalis, C. lari, C. helveticus and C. upsaliensis. Previously designed common primers, which can amplify the cdtB gene of C. jejuni, C. coli and C. fetus, were used for detecting seven Campylobacter species and differentiating between them by restriction digestion. The PCR-RFLP assay was validated with 277 strains, including 35 C. jejuni, 19 C. coli, 20 C. fetus, 24 C. hyointestinalis, 13 C. lari, 2 C. helveticus, 22 C. upsaliensis, 3 other Campylobacter spp. and 17 other species associated with human diseases. Sensitivity and specificity of the PCR-RFLP assay were 100 % except for C. hyointestinalis (88 % sensitivity). Furthermore, the PCR-RFLP assay successfully detected and differentiated C. jejuni, C. coli and C. fetus in clinical and animal samples. The results indicate that the PCR-RFLP assay is useful for the detection and differentiation of seven Campylobacter species important for human and animal diseases.


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