Non-enzymatic glycation is a Maillard reaction that occurs spontaneously between glucose and proteins and results in the accumulation of advanced glycation end products (AGEs), which are believed to be one of the causes for age-related tissue damage. Fructosamine 3-kinase (FN3K) is an enzyme involved in the protein deglycation process by fructosyl phosphorylation, returning amino acid residues to their pristine state with 3-deoxyglucosone (3-DG) and inorganic phosphate as by-products. 3-DG is a very reactive electrophile that is even more potent at generating AGEs than glucose; therefore, inhibitors specific to FN3K have been suggested as a means to suppress 3-DG formation. Dyn-12 is a substrate mimicking inhibitor with an IC50 value of approximately 6 mM. We report a new hydrophobic competitive inhibitor with respect to fructolysine that has an IC50 of 1.7 mM. Drug Dev. Res. 67:448-455, 2006. ? 2006 Wiley-Liss, Inc.
