Festival de primavera 1985

Orquestra Simfònica del Gran Teatre del Liceu, dirigida per Heinz FrickePrograma de mà de l'òpera La Valquíria, de Richard Wagner, la qual va ser representada els dies 28 i 31 de maig i 2 de juny del 1985. Els cantants van ser Siegfried Jerusalem (Siegmund) ; Hans Tschammer, Kurt Rydl i Aage Haugland (Hunding) ; Hans Kiemer (Wotan) ; Sabine Haas i Carmen Reppel (Sieglinde) ; Lia Frey-Rabine (Brünnhilde) ; Nadine Denize (Fricka) ; Linda plech (Gerhilde) ; Helga Thieme (Ortlinde) ; Mariana Cioromila (Waltraute) ; Anna Gonda (Schwertleite) ; Nancy Johnson (Helmwige) ; Heide Rabal (Segrune) ; Karen Johnson (Grimgerde) ; Brigitta Wutscher (Rossweisse). L'orquestra estava dirigida per Heinz Frick

Chemical Interrogation of FOXO3a Nuclear Translocation Identifies Potent and Selective Inhibitors of Phosphoinositide 3-Kinases*

Activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is one the most frequent genetic events in human cancer. A cell-based imaging assay that monitored the translocation of the Akt effector protein, Forkhead box O (FOXO), from the cytoplasm to the nucleus was employed to screen a collection of 33,992 small molecules. The positive compounds were used to screen kinases known to be involved in FOXO translocation. Pyrazolopyrimidine derivatives were found to be potent FOXO relocators as well as biochemical inhibitors of PI3Kα. A combination of virtual screening and molecular modeling led to the development of a structure-activity relationship, which indicated the preferred substituents on the pyrazolopyrimidine scaffold. This leads to the synthesis of ETP-45658, which is a potent and selective inhibitor of phosphoinositide 3-kinases and demonstrates mechanism of action in tumor cell lines and in vivo in treated mice