4RCH
Discovery of 2-Pyridyl Ureas as Glucokinase Activators
Summary for 4RCH
| Entry DOI | 10.2210/pdb4rch/pdb |
| Related | 4MLE 4MLH |
| Descriptor | Glucokinase, alpha-D-glucopyranose, 1-{3-[(2-ethylpyridin-3-yl)oxy]-5-(pyridin-2-ylsulfanyl)pyridin-2-yl}-3-methylurea, ... (4 entities in total) |
| Functional Keywords | transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 53587.83 |
| Authors | Voegtli, W.,Vigers, G.P.A. (deposition date: 2014-09-16, release date: 2014-10-08, Last modification date: 2023-09-20) |
| Primary citation | Hinklin, R.J.,Aicher, T.D.,Anderson, D.A.,Baer, B.R.,Boyd, S.A.,Condroski, K.R.,DeWolf, W.E.,Kraser, C.F.,McVean, M.,Rhodes, S.P.,Sturgis, H.L.,Voegtli, W.C.,Williams, L.,Houze, J.B. Discovery of 2-pyridylureas as glucokinase activators. J.Med.Chem., 57:8180-8186, 2014 Cited by PubMed Abstract: Glucokinase (GK) is the rate-limiting step for insulin release from the pancreas in response to high levels of glucose. Flux through GK also contributes to reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can allosterically activate GK may address this issue. Herein we report the identification and initial optimization of a novel series of glucokinase activators (GKAs). Optimization led to the identification of 33 as a compound that displayed activity in an oral glucose tolerance test (OGTT) in normal and diabetic mice. PubMed: 25203462DOI: 10.1021/jm501204z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
Download full validation report
