A patent review of glucokinase activators and disruptors of the glucokinase – glucokinase regulatory protein interaction: 2011 – 2014

Abstract

Introduction: Glucokinase (GK) is a key regulator of glucose homeostasis, and development of small molecule activators of this enzyme represents a promising new approach for the treatment of type 2 diabetes mellitus.

Areas covered: This manuscript reviews small molecule patent disclosures between late 2011 and February 2014 for both GK activators (GKAs) and GK−glucokinase regulatory protein (GK−GKRP) disruptors. The review is organized by company and structural class.

Expert opinion: The field of GKA research continues to progress, driven by research across many organizations. To date, > 20 candidates have entered clinical development with the most advanced in Phase II trials. Despite promising efficacy, a significant number of early candidates have been discontinued for various reasons including increased risk of hypoglycemia and lack of durability. Recent work in the field has focused on liver-selective activators, which have shown lower hypoglycemia risk, including the development of novel GK-GKRP disruptors that act to indirectly increase hepatic GK activity.

Keywords::

• glucokinase
• glucokinase activator
• glucokinase regulatory protein

Notes

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