title: A patent review of glucokinase activators and disruptors of the glucokinase--glucokinase regulatory protein interaction: 2011-2014.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Filipski
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Pfefferkorn
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D005941:Glucokinase / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology; D010330:Patents as Topic
chemical_list: D002352:Carrier Proteins; D007004:Hypoglycemic Agents; C080906:glucokinase regulatory protein; D005941:Glucokinase; D005947:Glucose
keywords: glucokinase; glucokinase activator; glucokinase regulatory protein