This week in therapeutics




Licensing status

Publication and contact information

Endocrine/metabolic disease


Glucokinase (GCK; GK); glucokinase regulator (GCKR; GKRP)

In vitro and mouse studies identified compounds that could help treat type 2 diabetes by binding GKRP and disrupting its interaction with GK. A high throughput screen and additional structural optimization identified a compound that bound GKRP and promoted the disassociation of the GK-GKRP complex with an IC50 of 7 nM. In three diabetic mouse models, a structurally related compound decreased blood glucose levels compared with vehicle. The compound did not reduce glucose levels in normal mice. Next steps include studying the effect of these compounds on the metabolic physiology of the liver.
At least nine companies have GK activators in Phase II
or earlier development to treat type 2 diabetes. In October, Amgen Inc. returned rights to the GK activator ARRY-403 (formerly AMG151) to Array BioPharma Inc. The compound had completed Phase II testing in type 2 diabetes (see Glucokinase alternative, page 1).

SciBX 6(45); doi:10.1038/scibx.2013.1291
Published online Nov. 21, 2013

Patent application filed; licensing status undisclosed

Lloyd, D.J. et al. Nature;
published online Nov. 13, 2013;
Contact: David J. Lloyd, Amgen Inc., Thousand Oaks, Calif.
Contact: Clarence Hale, same affiliation as above