Novel idebenone analogs block Shc’s access to insulin receptor to improve insulin sensitivity

• Published in: Biomedicine & pharmacotherapy Vol. 132; p. 110823
• Main Authors: Hui, ChunKiu, Tomilov, Alexey, Garcia, Chase, Jiang, XiaoSong, Fash, David M., Khdour, Omar M., Rosso, Cristian, Filippini, Giacomo, Prato, Maurizio, Graham, James, Hecht, Sidney, Havel, Peter, Cortopassi, Gino
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.12.2020
• Subjects: Animals; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; Drug discovery; Insulin - metabolism; Insulin Resistance; Mice; Mice, Inbred C57BL; Novel insulin sensitizing agents; Rats; Rats, Sprague-Dawley; Receptor, Insulin - metabolism; Shc blockers; Small molecule therapeutics; Src Homology 2 Domain-Containing, Transforming Protein 1 - genetics; Structure-Activity Relationship; Type 2 Diabetes; Ubiquinone - analogs & derivatives; Ubiquinone - chemistry; Ubiquinone - pharmacology; Shc blockers; Drug discovery; Small molecule therapeutics; Novel insulin sensitizing agents; Type 2 Diabetes

[Display omitted] •Idebenone drug engagement of p52Shc protein regulates insulin sensitivity.•Analogs of idebenone engage p52Shc and insulin-sensitizer differentially.•One analog is a more potent insulin sensitizer than idebenone itself.•Idebenone metabolites engage p52Shc and insulin sensitize. The...