Fructose-1,6-bisphosphatase inhibitors: A new valid approach for management of type 2 diabetes mellitus

Abstract

The rising incidence of diabetes and confines allied with clinical therapies emphasized the need to explore new molecular targets to develop novel, effective and safer antihyperglycemic agents. Excessive endogenous glucose production by gluconeogenesis is a primary determinant of hyperglycemia in patients with type 2 diabetes. But not even a single current medication acts directly to reduce gluconeogenesis. Fructose-1,6-bisphosphatase (FBPase), a well recognized rate controlling enzyme of gluconeogenesis, has emerged as legitimate molecular level target to control gluconeogenesis mediated glucose overproduction and its inhibitors are likely to fulfill an unmet medical need. In this compilation various chemical classes of FBPase inhibitors have been reviewed which mainly acts through uncompetitive and non-competitive manner. A detailed account on structure activity relationship studies of inhibitors have been presented along with their molecular level interactions at binding sites of enzyme. Three Dimensional Quantitative Structure Activity relationship (3D-QSAR) studies, performed to optimize the lead, have been summarized at some places. In this assemblage, FBPase inhibitors patented in past have been compiled in tabular form. This review highlights the new insight into the therapeutic utility of FBPase inhibitors and their potential as a new class of antidiabetic drugs.

Keywords: Diabetes; Fructose-1,6-bisphosphatase; Gluconeogenesis; Glucose; Inhibitor; QSAR.