Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase

…, Z Zhao, S Gallion, JA Whitney, D Maclin…

文献索引：Currie, Kevin S.; Kropf, Jeffrey E.; Lee, Tony; Blomgren, Peter; Xu, Jianjun; Zhao, Zhongdong; Gallion, Steve; Whitney, J. Andrew; Maclin, Deborah; Lansdon, Eric B.; Maciejewski, Patricia; Rossi, Ann Marie; Rong, Hong; Macaluso, Jennifer; Barbosa, James; Di Paolo, Julie A.; Mitchell, Scott A. Journal of Medicinal Chemistry, 2014 , vol. 57, # 9 p. 3856 - 3873

全文：HTML全文

被引用次数: 40

摘要

Spleen tyrosine kinase (Syk) is an attractive drug target in autoimmune, inflammatory, and oncology disease indications. The most advanced Syk inhibitor, R406, 1 (or its prodrug form fostamatinib, 2), has shown efficacy in multiple therapeutic indications, but its clinical progress has been hampered by dose-limiting adverse effects that have been attributed, at least in part, to the off-target activities of 1. It is expected that a more selective Syk inhibitor ...