8-O-methylsclerotiorinamine, antagonist of the Grb2-SH2 domain, isolated from Penicillium multicolor

A new secondary metabolite, 8-O-methylsclerotiorinamine (1), was isolated from a strain of Penicillium multicolor, and its structure was established using NMR spectroscopy and chemical evidence. The metabolite inhibited significantly the binding between the Grb2-SH2 domain and the phosphopeptide derived from the Shc protein and also blocked the protein-protein interactions of Grb2-Shc in cell-based experiments, with IC50 values of 5.3 and 50 mu M, respectively.