2. Academic Validation
  3. Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase

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

  • J Med Chem. 2014 May 8;57(9):3856-73. doi: 10.1021/jm500228a.
Kevin S Currie 1,  Jeffrey E Kropf,  Tony Lee,  Peter Blomgren,  Jianjun Xu,  Zhongdong Zhao,  Steve Gallion,  J Andrew Whitney,  Deborah Maclin,  Eric B Lansdon,  Patricia Maciejewski,  Ann Marie Rossi,  Hong Rong,  Jennifer Macaluso,  James Barbosa,  Julie A Di Paolo,  Scott A Mitchell
Affiliations

Affiliation

  • 1 Department of Chemistry, ‡Department of Biology, and §Department of Drug Metabolism, Gilead Sciences, Inc. , Branford, Connecticut 06405, United States.
PMID: 24779514 DOI: 10.1021/jm500228a
Abstract

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15968
    99.88%, Syk抑制剂
    Syk
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