Abstract 2599: Discovery and pharmacological characterization of the second generation of Btk inhibitors with improved target selectivity and enhanced in vivo efficacy

Author(s):  
Jiayin Zhang ◽  
Dong Liu ◽  
Ru Shen ◽  
Yinfa Yan ◽  
Liuqing Yang ◽  
...  
2016 ◽  
Vol 111 ◽  
pp. 208-216 ◽  
Author(s):  
Marta Calbet ◽  
Miriam Andrés ◽  
Clara Armengol ◽  
Mónica Bravo ◽  
Peter Eichhorn ◽  
...  

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200172
Author(s):  
Ya Zhang ◽  
Luis Alfonso Yañez Guerra ◽  
Michaela Egertová ◽  
Cleidiane G. Zampronio ◽  
Alexandra M. Jones ◽  
...  

Somatostatin (SS) and allatostatin-C (ASTC) are structurally and evolutionarily related neuropeptides that act as inhibitory regulators of physiological processes in mammals and insects, respectively. Here, we report the first molecular and functional characterization of SS/ASTC-type signalling in a deuterostome invertebrate—the starfish Asterias rubens (phylum Echinodermata). Two SS/ASTC-type precursors were identified in A. rubens (ArSSP1 and ArSSP2) and the structures of neuropeptides derived from these proteins (ArSS1 and ArSS2) were analysed using mass spectrometry. Pharmacological characterization of three cloned A. rubens SS/ASTC-type receptors (ArSSR1–3) revealed that ArSS2, but not ArSS1, acts as a ligand for all three receptors. Analysis of ArSS2 expression in A. rubens using mRNA in situ hybridization and immunohistochemistry revealed stained cells/fibres in the central nervous system, the digestive system (e.g. cardiac stomach) and the body wall and its appendages (e.g. tube feet). Furthermore, in vitro pharmacological tests revealed that ArSS2 causes dose-dependent relaxation of tube foot and cardiac stomach preparations, while injection of ArSS2 in vivo causes partial eversion of the cardiac stomach. Our findings provide new insights into the molecular evolution of SS/ASTC-type signalling in the animal kingdom and reveal an ancient role of SS-type neuropeptides as inhibitory regulators of muscle contractility.


2016 ◽  
Vol 791 ◽  
pp. 115-123 ◽  
Author(s):  
Alessandra Porcu ◽  
Carla Lobina ◽  
Daniela Giunta ◽  
Maurizio Solinas ◽  
Claudia Mugnaini ◽  
...  

2007 ◽  
Vol 193 (1) ◽  
pp. 121-136 ◽  
Author(s):  
Linda M. Rorick-Kehn ◽  
Bryan G. Johnson ◽  
Karen M. Knitowski ◽  
Craig R. Salhoff ◽  
Jeffrey M. Witkin ◽  
...  

1996 ◽  
Vol 32 (1-3) ◽  
pp. 111-114 ◽  
Author(s):  
Luciana Bizeto ◽  
Edson Antunes ◽  
Fernanda C.V. Portaro ◽  
Maria Aparecida Juliano ◽  
Luiz Juliano ◽  
...  

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