Glucose-phosphorylating enzyme, glucokinase (GK) plays a major role in glucose homeostasis primarily
through its regulatory actions in pancreatic β-cells and liver hepatocytes. Conversion of glucose to glucose-6-phosphate
by GK promotes glycogen synthesis in liver hepatocytes, and insulin release in the pancreatic β-cells. Small molecules
called glucokinase activators (GKAs) which bind to an allosteric activator site of the GK enzyme have indeed been
discovered and developed, and thus hold great promise as new, effective and safe antidiabetic agents. GKAs enhance the
catalytic activity of GK and promising clinical trials in humans demonstrated that they are highly useful in the treatment
of type 2 diabetes mellitus. Most of the reported GKAs include amide derivatives like benzamides, acrylamides,
carboxamides, acetamides and acrylamides. Examples include Piragliatin, AZD1656, AZD6370, R1440 GKA2, GKA 50,
YH GKA, PSN 010, and LY2121260. Recent findings on GKAs including lead compounds and overview of current
hypothesis on mechanism of GK activation along with summary of the recently published patents as well as the GKAs of
natural origin are reported in the present review.
Benzamides, Diabetes mellitus, Glucokinase, Glucokinase activators, T2DM.
Department of Pharmaceutical Chemistry, JCDM College of Pharmacy, Barnala Road, Sirsa-125055, India.