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Expert Opin Ther Pat. 2014 Aug;24(8):875-91. doi: 10.1517/13543776.2014.918957. Epub 2014 May 12.

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

Author information

1
Cardiovascular, Metabolic & Endocrine Diseases Chemistry, Pfizer Worldwide Research & Development , 610 Main St, Cambridge, MA 02139 , USA +1 617 551 3267 ; +1 617 551 3082 ; kevin.filipski@pfizer.com.

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

PMID:
24821087
DOI:
10.1517/13543776.2014.918957
[Indexed for MEDLINE]

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