Abstract
Glucokinase activator is expectedly associated with a dual mechanism for lowering blood glucose concentration by the enhancement of glucose uptake in the liver and insulin secretion from pancreatic beta cell. Therefore, glucokinase has been an attractive target for anti-diabetic therapy. Novel benzamide derivatives were synthesized and tested using in vitro assays by measuring fold increase of glucokinase activity at 5.0 mM glucose concentration. Among the prepared compounds, YH-GKA was found to be an active glucokinase activator with EC50 of 70 nM and glucose area under the curve reduction of 29.6% at 50 mg/kg in an oral glucose tolerance test. In a subchronic study with ob/ob mice, YH-GKA showed significant decrease in blood glucose levels and no adverse effects on serum lipids or body weight. Overall, YH-GKA is a promising candidate for the therapy of type 2 diabetes mellitus.
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Kaapjoo Park, PhD Director, Yuhan Research Institute, Yuhan Corporation
1983∼1987 Seoul National University, Chemistry, BA
1988∼1990 POSTEH, Polymer Chemistry, MS
1992∼1997 Brown University, Organic Chemistry, PhD
1997∼2001 Texas A&M University & Duke University
2001∼2010 Wyeth/Pfizer, Inc. USA
Main Research Areas
Organic Chemistry, Medicinal Chemistry, Drug Discovery
Oncology, Inflammation, Metabolic Disease
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Park, K. Identification of YH-GKA, a novel benzamide glucokinase activator as therapeutic candidate for type 2 diabetes mellitus. Arch. Pharm. Res. 35, 2029–2033 (2012). https://doi.org/10.1007/s12272-012-1201-9
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DOI: https://doi.org/10.1007/s12272-012-1201-9