1,720,974 research outputs found
Small molecules modulation of 14-3-3 protein–protein interactions
No full text14-3-3 is a family of highly conserved regulatory proteins which is attracting a significant interest due to its potential role as target for pharmacological intervention against cancer and neurodegenerative disorders. Although modulating protein-protein interactions (PPI) is still conceived as a challenging task in drug discovery, in past few years peptide inhibitors and small molecular modulators of 14-3-3 PPI have been described. Here we examine structural and biological features of 14-3-3 and propose an overview on techniques used for discovering small molecular inhibitors and stabilizers of 14-3-3 PPI
Preparation of 4-amino-substituted pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine derivative as the Src family kinases
No full textThe present invention refers to 4-amino-substituted pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine derivs. of formula I able to target the Src family kinases (SFKs) such as Src, Fyn and Hck tyrosine kinases as well as Abl tyrosine kinase and uses and method of prepn. thereof, wherein Z = CH or N; R2 = alkyl; Y = NH, O or S; X = CH or N; W = NH, NCH3 or S; n = 0-4; m = 0-1; R3 = H or aralkyl; R4 = substituted Ph. In particular, the compds. of the invention are for use in the treatment and/or prevention of cancer, such as neuroblastoma (NB) or glioblastoma multiform (GBM) or for use in the treatment and/or prevention of neurodegenerative diseases such as taupathies. Thus, e.g., II was prepd. and showed EC50 value of 0.20 μM against c-Src and 0.15 μM against Abl in enzymic activity assay
COMPOUNDS AND USES THEREOF
No full textThe present invention refers to 4-amino-substituted pyrazolo[3,4-d]pyrimidine and
pyrrolo[2,3-d]pyrimidine derivatives of formula I and IV able to target the Src family
kinases (SFKs) such as Src, Fyn and Hck tyrosine kinases as well as Abl tyrosine
kinase and uses and method of preparation thereof. In particular, the compounds of the
invention are for use in the treatment and/or prevention of cancer, such as
neuroblastoma (NB) or glioblastoma multiforme (GBM) or for use in the treatment
and/or prevention of neurodegenerative diseases such as taupathie
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Molecular insights to the bioactive form of BV02, a reference inhibitor of 14-3-3σ protein-protein interactions
No full textBV02 is a reference inhibitor of 14-3-3 protein-protein interactions, which is currently used as chemical biology tool to understand the role of 14-3-3 proteins in pathological contexts. Due to chemical instability in certain conditions, its bioactive form has remained unclear. Here, we use NMR spectroscopy to prove for the first time the direct interaction between the molecule and 14-3-3σ, and to depict its bioactive form, namely the phthalimide derivative 9. Our work provides molecular insights to the bioactive form of the 14-3-3 PPI inhibitor and facilitates further development as candidate therapeutic agent
Hit Recycling: Discovery of a Potent Carbonic Anhydrase Inhibitor by in Silico Target Fishing
No full textIn silico target fishing is an emerging tool in drug discovery, which is mostly used for primary target or off-target prediction and drug repositioning. In this work, we developed an in silico target fishing protocol to identify the primary target of GV2-20, a false-positive hit highlighted in a cell-based screen for 14-3-3 modulators. Although GV2-20 does not bind to 14-3-3 proteins, it showed remarkable antiproliferative effects in CML cells, thus raising interest toward the identification of its primary target. Six potential targets of GV2-20 were prioritized in silico and tested in vitro. Our results show that the molecule is a potent inhibitor of carbonic anhydrase 2 (CA2), thus confirming the predictive capability of our protocol. Most notably, GV2-20 experienced a remarkable selectivity for CA2, CA7, CA9, and CA12, and its scaffold was never explored before as a chemotype for CA inhibition, thus becoming an interesting lead candidate for further development
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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