Ganodermycin, a novel inhibitor of CXCL10 expression from Ganoderma applanatum

CXCL10 (inducible protein-10) is a highly inducible chemoattractant, which contributes to the recruitment of inflammatory cells, such as macrophages and T-lymphocytes, and thereby has important roles in chronic inflammatory conditions. In a search for new inhibitors of CXCL10 expression in MonoMac6 cells, a novel compound, designated as Ganodermycin, was isolated from fermentations of the basidiomycete Ganoderma applanatum. The structure was determined by a combination of spectroscopic techniques. Ganodermycin inhibited the lipopolysaccharide (LPS)/interferon (IFN)-gamma-induced CXCL10 promoter activity in transiently transfected MonoMac6 cells in a dose-dependent manner with IC(50) values of 15-20 mu g ml(-1) (53-71 mu M). Ganodermycin also reduced LPS/IFN-gamma-induced CXCL10 protein synthesis and excretion. The Journal of Antibiotics (2011) 64, 683-686; doi:10.1038/ja.2011.64; published online 27 July 2011