In Vitro Selection of Anti-Akt2 Thioether-Macrocyclic Peptides Leading to Isoform-Selective Inhibitors

• Published in: ACS chemical biology Vol. 7; no. 3; pp. 607 - 613
• Main Authors: Hayashi, Yuuki, Morimoto, Jumpei, Suga, Hiroaki
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.03.2012
• Subjects: Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Humans; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Macrocyclic Compounds - chemical synthesis; Macrocyclic Compounds - chemistry; Macrocyclic Compounds - pharmacology; Models, Molecular; Molecular Structure; Peptides - chemical synthesis; Peptides - chemistry; Peptides - pharmacology; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Structure-Activity Relationship; Sulfides - chemical synthesis; Sulfides - chemistry; Sulfides - pharmacology

The Akt kinase family, consisting of three isoforms in humans, is a well-validated class of drug target. Through various screening campaigns in academics and pharmaceutical industries, several promising inhibitors have been developed to date. However, due to the mechanistic and structural similariti...