Discovery of fructose-1,6-bisphosphatase inhibitors for the treatment of type 2 diabetes.
Overproduction of glucose via gluconeogenesis is a principal cause of the high blood glucose levels found in patients with type 2 diabetes, and is inadequately controlled by currently available medications. The enzyme fructose-1,6-bisphosphatase (FBPase), a major control point in the pathway of gluconeogenesis, is recognized as an attractive target for pharmacological intervention. This review describes recent progress in the discovery and optimization of inhibitors of FBPase, with emphasis on non-competitive inhibitors that interact with the adenosine monophosphate site of the enzyme. The biological characterization of the most advanced of these drugs, CS-917, is also summarized.
van Poelje
Paul D
PD
Department of Biological Sciences, Metabasis Therapeutics Inc, 11119 North Torrey Pines Road, La Jolla, CA 92037, USA. PaulV@mbasis.com.
Dang
Qun
Q
Erion
Mark D
MD
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D006597:Fructose-Bisphosphatase / Q000187:drug effects* / Q000378:metabolism; D006801:Humans
D004791:Enzyme Inhibitors; D006597:Fructose-Bisphosphatase