Glucokinase activators.
In this review we highlight recently disclosed progress in the field of small-molecule activators of the human glucokinase enzyme. Several of the reported chemotypes possess structural features that diverge from known leads; some of these modifications appear to be specifically designed to modulate tissue selectivity or discrete parameters of enzyme function (e.g., S0.5 v Vmax). This review will inform the reader of the extent of continued effort being directed toward discovery of a first-in-class drug for Type II diabetes mellitus that functions through this target. Patents were selected from those published in December 2009 up to November 2011; foreign filings were translated where possible to understand the claims and biological techniques utilized to characterize the reported glucokinase activators. Overall, there appears to be a recent trend leading to reduced patent filings for small-molecule glucokinase activators. There are many possible explanations for this trend; however, it is likely that the field has reached maturity and that the downturn of new disclosures represents the transition of many of these programs to the clinic.
Cardiovascular, Metabolic & Endocrine Disease Research, Pfizer Worldwide Research & Development, Cambridge, MA 02139, USA.
Kevin J
KJ
Filipski
Kentaro
K
Futatsugi
Jeffrey A
JA
Pfefferkorn
Benjamin D
BD
Stevens
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D015195:Drug Design; D020536:Enzyme Activators / Q000494:pharmacology; D005941:Glucokinase / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D010330:Patents as Topic
D020536:Enzyme Activators; D007004:Hypoglycemic Agents; D005941:Glucokinase