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

被引：36

作者：

Filipski, Kevin J. ^{[1
]}

Pfefferkorn, Jeffrey A. ^{[1
]}

机构：

[1] Pfizer Worldwide Res & Dev, Cardiovasc Metab & Endocrine Dis Chem, Cambridge, MA 02139 USA

来源：

EXPERT OPINION ON THERAPEUTIC PATENTS | 2014年 / 24卷 / 08期

关键词：

glucokinase; glucokinase activator; glucokinase regulatory protein; TYPE-2; DIABETES-MELLITUS; SMALL-MOLECULE DISRUPTORS; HEPATIC GLUCOKINASE; CLINICAL CANDIDATE; ALLOSTERIC ACTIVATORS; SCALABLE SYNTHESIS; EUGLYCEMIC CLAMP; GLUCOSE; DISCOVERY; AZD1656;

D O I：

10.1517/13543776.2014.918957

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：875 / 891

页数：17

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