4ISE

Human glucokinase in complex with novel activator (2S)-3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(1,3-thiazol-2-yl)propanamide

Summary for 4ISE

• Entry DOI: 10.2210/pdb4ise/pdb
• Related: 4ISF 4ISG
• Descriptor: Glucokinase, alpha-D-glucopyranose, (2S)-3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(1,3-thiazol-2-yl)propanamide, ... (5 entities in total)
• Functional Keywords: transferase/activator activity, glucose conversion to g6p, phosphorylation, transferase-transferase activator complex, transferase/transferase activator
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 52100.06

Authors

Hosfield, D.,Skene, R.J. (deposition date: 2013-01-16, release date: 2013-03-20, Last modification date: 2024-02-28)

Primary citation

Cheruvallath, Z.S.,Gwaltney, S.L.,Sabat, M.,Tang, M.,Feng, J.,Wang, H.,Miura, J.,Guntupalli, P.,Jennings, A.,Hosfield, D.,Lee, B.,Wu, Y.
Design, synthesis and SAR of novel glucokinase activators.
Bioorg.Med.Chem.Lett., 23:2166-2171, 2013

PubMed Abstract: Guided by co-crystal structures of compounds 15, 22 and 30, an SBDD approach led to the discovery of the 6-methyl pyridone series as a novel class of GKAs that potently activate GK in enzyme and cell assays. Anti-diabetic OGTT efficacy was demonstrated with 54 in a mouse model of type 2 diabetes.

PubMed: 23434031
DOI: 10.1016/j.bmcl.2013.01.093

Experimental method

X-RAY DIFFRACTION (1.78 Å)