4 research outputs found
In Silico Identification of a Novel Hinge-Binding Scaffold for Kinase Inhibitor Discovery
To explore novel kinase hinge-binding
scaffolds, we carried out
structure-based virtual screening against p38α MAPK as a model
system. With the assistance of developed kinase-specific structural
filters, we identify a novel lead compound that selectively inhibits
a panel of kinases with threonine as the gatekeeper residue, including
BTK and LCK. These kinases play important roles in lymphocyte activation,
which encouraged us to design novel kinase inhibitors as drug candidates
for ameliorating inflammatory diseases and cancers. Therefore, we
chemically modified our substituted triazole-class lead compound to
improve the binding affinity and selectivity via a “minimal
decoration” strategy, which resulted in potent and selective
kinase inhibitors against LCK (18 nM) and BTK (8 nM). Subsequent crystallographic
experiments validated our design. These rationally designed compounds
exhibit potent on-target inhibition against BTK in B cells or LCK
in T cells, respectively. Our work demonstrates that structure-based
virtual screening can be applied to facilitate the development of
novel chemical entities in crowded chemical space in the field of
kinase inhibitor discovery
Comments on a notorious verdict : the trial of Lula
Comments on a notorious verdict: The trial of Lula might be the most important judicial document published in Brazil for decades. The present selection of articles came to exist after a spontaneous movement, and significant enough as well, of Brazilian and foreign lawyers who carefully verified the verdict rendered in the extent of the procedure which was processed at the 13ª Vara Federal de Curitiba, in the case that was known at the media as the Guarujá triplex.
From the Introduction by Geraldo Prad
Comentários a uma sentença anunciada : o processo Lula
Comentários a uma sentença: o Caso Lula é talvez o mais importante documento jurídico publicado no Brasil em décadas. A presente coletânea de artigos nasceu de um movimento espontâneo e bastante significativo de juristas brasileiros e estrangeiros que examinaram cuidadosamente a sentença proferida no âmbito do processo que tramitou na 13ª Vara Federal de Curitiba, no caso que ficou conhecido na mídia como o do tríplex do Guarujá.
<br>De la presentación de Geraldo Prad
Comentarios a una sentencia anunciada : el proceso Lula
El centenar de textos que conforman este libro -escritos por un movimiento de prestigiosos/as juristas y abogados- desgranan el procedimiento al que fue sometido Lula. En la opinión de las y los autores de los artículos las normas no fueron observadas, y su inobservancia llevó a que se dictaminase una decisión injusta.
Frases del estilo "Voy a tomar una decisión revolucionaria, dejando de lado la ley, porque por la ley no se puede condenarlo de ninguna manera, dichas en los juicios por las más altas autoridades judiciales militares y civiles, hoy son conocidas gracias a quienes se abocaron al trabajo de escuchar los audios de aquellas sesiones, nutriendo las reflexiones que argumentan sobre el imperativo de la hora: restablecer el estado de derecho y absolver al presidente Lula Da Silva