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Bromodomänen …… sind eine neuartige Klasse von Zielproteinen für epigenetische Wirkstoffe. D. J. Dixon, P. E. Brennan et al. berichten in ihrer Zuschrift auf S. 845 über die erste potente, selektive, zellgängige und zellaktive chemische Sonde für die PCAF‐Bromodomäne. Die Sonde, bezeichnet als L‐Moses, wurde durch eine Kombination von Dockingstudien, Inhibitordesign und asymmetrischer Synthese entwickelt...
The p300/CBP‐associated factor (PCAF) and related GCN5 bromodomain‐containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine‐based L‐45 (dubbed L‐Moses) as the first potent, selective, and cell‐active PCAF bromodomain (Brd) inhibitor...
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