S100A9-clot not, bleed not

Although the new generation of antithrombotic drugs provides marked improvements over warfarin, they all still carry bleeding risk. S100 calcium binding protein A9 could represent a new target that, when blocked, prevents thrombosis without increasing that risk.1

The new findings from U.S. researchers may hand a new indication to at least two companies-InflammatoRx Inc. and Active Biotech AB-developing inhibitors of this S100 protein to treat cancer, autoimmune diseases and inflammation.

S100 proteins are a family of signaling molecules whose individual members play multiple roles in many cells and tissue types. S100 calcium binding protein A9 (S100A9; calgranulin B; MRP14) is expressed by neutrophils and monocytes and is activated by endothelial, epithelial and synovial cells.

Although its intracellular functions are poorly understood, secreted S100A9 can stimulate the production of proinflammatory cytokines by monocytes and promote the migration and adhesion of neutrophils and monocytes to sites of inflammation.

S100A9 frequently occurs as a heterodimer with S100A8 (calgranulin A; MRP8), whose function requires S100A9 to bind and stabilize it.

In 2006 and 2008, teams led by Daniel Simon identified an S100A8/S100A9 heterodimer expressed by

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