1043962-60-2Relevant academic research and scientific papers
Structural and chemical insights into the covalent-allosteric inhibition of the protein kinase Akt
Uhlenbrock, Niklas,Smith, Steven,Weisner, J?rn,Landel, Ina,Lindemann, Marius,Le, Thien Anh,Hardick, Julia,Gontla, Rajesh,Scheinpflug, Rebekka,Czodrowski, Paul,Janning, Petra,Depta, Laura,Quambusch, Lena,Müller, Matthias P.,Engels, Bernd,Rauh, Daniel
, p. 3573 - 3585 (2019/03/28)
The Ser/Thr kinase Akt (Protein Kinase B/PKB) is a master switch in cellular signal transduction pathways. Its downstream signaling influences cell proliferation, cell growth, and apoptosis, rendering Akt a prominent drug target. The unique activation mechanism of Akt involves a change of the relative orientation of its N-terminal pleckstrin homology (PH) and the kinase domain and makes this kinase suitable for highly specific allosteric modulation. Here we present a unique set of crystal structures of covalent-allosteric interdomain inhibitors in complex with full-length Akt and report the structure-based design, synthesis, biological and pharmacological evaluation of a focused library of these innovative inhibitors.
QUINAZOLINONE AND FUSED PYRIMIDINONE COMPOUNDS AND THEIR USE IN TREATING SODIUM CHANNEL-MEDIATED DISEASES OR CONDITIONS
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Page/Page column 107, (2008/12/07)
This invention is directed to compounds of formula (I): wherein (A), n, R1, R2 and R3 are as defined herein, as a stereoisomer, enantiomer, tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.
