Schizophyllan (SPG / Sonifilan / Sizofiran)

Schizophyllan is a high-molecular-weight (1->3)-beta-D-glucan with beta-(1->6)-linked D-glucose branches at every third residue in the main chain. In aqueous solution, three individual polysaccharide chains wind around each other to form a rigid triple-helix structure (persistence length ~180 nm, pitch 0.30 nm per glucose residue) that is essential for biological activity — denaturation of the helix abolishes immunostimulatory properties. The triple helix binds to dectin-1 and complement receptor 3 (CR3) on macrophages and dendritic cells, triggering receptor clustering and activation of Syk kinase, CARD9, and downstream NF-kB and MAPK signaling. This induces secretion of pro-inflammatory cytokines (IL-1beta, IL-6, IL-12, TNF-alpha, IFN-gamma), enhances antigen presentation, stimulates B-lymphocyte proliferation, activates complement cascade, and potentiates NK cell and cytotoxic T-lymphocyte (CTL) tumor-killing activity.