molecules of the month

Context.BMS-820132 (Bristol Myers Squibb) is an oral glucokinase (GK) partial activator intended for diabetes. GK activators for diabetes were hotly pursued in the late 2000’s, with well over 100 industry patents on GK activators by 2009. The pursuit was triggered by the discovery of the first allosteric activators of glucokinase from an enzymatic screen of 120k compounds at Roche in 2003, leading to the first GK activator studied in diabetes patients. Initial clinical glucokinase full activators were challenged by hypoglycemia and loss of efficacy over time, leading to alternative strategies such as hepatoselective molecules, and the partial activation approach employed here. Target. Unlike protein kinases, glucokinase (GK, hexokinase IV) phosphorylates glucose to glucose-6-phosphate. GK is not saturated at physiological glucose…