GLUCOKINASE ACTIVATORS AS POTENTIAL ANTIDIABETIC AGENTS POSSESSING SUPERIOR GLUCOSE-LOWERING EFFICACY

摘要

Currently marketed drugs for type 2 diabetes do not provide adequate glucose control over the long term. Hence, there is still a significant unmet medical need for novel agents that modulate glucose levels with greater and longer-lasting efficacy. Results from several recent studies, including emerging clinical data, have demonstrated that small-molecule glucokinase activators may be able to fill this void. The glucose-sensing enzyme glucokinase plays a pivotal role in whole-body glucose homeostasis through actions in multiple organs, most notably in the liver and pancreas. Clucokinase activators raise the enzyme's activity by increasing its velocity and its affinity for glucose, effects that can result in exquisite glucose lowering when translated into the in vivo setting. Many pharmaceutical companies have initiated drug discovery programs in the area and, in recent years, several organizations have progressed glucokinase activators into clinical trials as potential antidi-abetic agents. This review summarizes key pharmacological data associated with several of the leading classes of small-molecule glucokinase activators.