R406

R406 is a small-molecule tyrosine kinase inhibitor that selectively inhibits spleen tyrosine kinase (Syk). It is the pharmacologically active metabolite of the oral prodrug fostamatinib (fostamatinib disodium). Upon administration, fostamatinib is rapidly converted to R406, which mediates the drug’s clinical effects through Syk blockade.

Mechanism of action: R406 inhibits Syk-dependent signaling pathways, dampening the activation of Fc gamma receptor and B-cell receptor signaling in immune cells. As a result, it can reduce antibody-dependent cellular activation, inflammatory cytokine release, and platelet destruction in autoimmune contexts.

Clinical development: R406 has been studied in preclinical models and early-stage human trials for autoimmune diseases such as immune thrombocytopenia (ITP) and rheumatoid arthritis, among others. It is not marketed as a stand-alone drug; the approved product is fostamatinib, a prodrug that delivers R406 in vivo. Fostamatinib was approved by regulatory agencies for certain indications (notably chronic ITP in some regions) based on its Syk-inhibitory activity.

Pharmacology and status: R406 itself is used mainly as a research tool and pharmacological reference compound; it is not approved as a prescription medication. Its activity can extend to other kinases at higher concentrations, but its primary target is Syk.