Bifunctional inhibitors of mevalonate kinase and mevalonate 5-diphosphate decarboxylase.
[structure: see text] A bifunctional inhibitor of mevalonate kinase and mevalonate 5-diphosphate decarboxylase was synthesized. Both enzymes are in the cholesterol biosynthetic pathway and play an important role in regulating cholesterol biosynthesis. The molecule may become a useful lead compound for further development for treating cardiovascular disease and cancer. This study provides a novel example of a single inhibitor blocking two sequential steps simultaneously in the cholesterol biosynthetic pathway.
Qiu
Yongge
Y
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, P. R. China.
Li
Ding
D
D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002784:Cholesterol / Q000096:biosynthesis*; D008798:Mevalonic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*
C046285:5-diphosphomevalonic acid; D002784:Cholesterol; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D002262:Carboxy-Lyases; C022503:pyrophosphomevalonate decarboxylase; D008798:Mevalonic Acid