Amide-to-Ester Substitution as a Strategy for Optimizing PROTAC Permeability and Cellular Activity

Criteria for predicting the druglike properties of “beyond Rule of 5” Proteolysis Targeting Chimeras (PROTAC) degraders are underdeveloped. PROTAC components are often combined via amide couplings due to their reliability. Amides, however, can give rise to poor absorption, distribution, metabolism,...

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Veröffentlicht in:	Journal of medicinal chemistry 2021-12, Vol.64 (24), p.18082-18101
Hauptverfasser:	Klein, Victoria G, Bond, Adam G, Craigon, Conner, Lokey, R. Scott, Ciulli, Alessio
Format:	Artikel
Sprache:	eng
Schlagworte:	Amides - chemistry Animals Cell Membrane Permeability Dogs Esters - chemistry Hydrogen Bonding Ligands Madin Darby Canine Kidney Cells Oligopeptides - chemistry Oligopeptides - metabolism Oligopeptides - pharmacology Proteolysis - drug effects Reproducibility of Results Ubiquitin-Protein Ligases - metabolism
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