1266480-49-2Relevant academic research and scientific papers
Discovery of potent nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) inhibitors with ancillary carbonic anhydrase inhibition for cancer (immuno)therapy
Boshta, Nader M.,Bua, Silvia,Lee, Sang-Yong,Mirza, Salahuddin,Namasivayam, Vigneshwaran,Perotti, Arianna,Supuran, Claudiu T.,Müller, Christa E.
, p. 1187 - 1206 (2021/10/27)
Nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) catalyzes the hydrolysis of extracellular nucleotides. It is expressed by immune cells and some carcinomas,e.g.of kidney and colon. Together with ecto-5′-nucleotidase (CD73), NPP3 produces immunosuppres
Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase
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.
, p. 3856 - 3873 (2014/05/20)
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 would provide a greater therapeutic window. Herein we report the discovery and optimization of a novel series of imidazo[1,2-a]pyrazine Syk inhibitors. This work culminated in the identification of GS-9973, 68, a highly selective and orally efficacious Syk inhibitor which is currently undergoing clinical evaluation for autoimmune and oncology indications.
