The identification, synthesis and SAR of a novel series of glucokinase activators is described. The interplay between lipophilicity, potency and physical properties is discussed, and compound 22 highlighted as having a suitable balance. In vivo pharmacokinetic and acute efficacy studies on this compound are also presented.
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http://dx.doi.org/10.1016/j.bmcl.2005.01.087 | DOI Listing |
In Silico Pharmacol
January 2025
Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam 786004 India.
Unlabelled: Globally, there is an increase in the prevalence of metabolic illnesses, including diabetes mellitus. However, current therapies for diabetes and other metabolic illnesses are not well understood. Pharmacological treatment of type 2 diabetes is challenging, moreover, the majority of antidiabetic medications are incompatible with individuals who have cardiac disease, renal illness, or liver damage.
View Article and Find Full Text PDFTrends Biochem Sci
January 2025
Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, Denmark. Electronic address:
Human glucokinase (GCK) functions as a glucose sensor in the pancreas and liver, where GCK activity regulates insulin secretion and glycogen synthesis, respectively. GCK's low affinity for glucose and the sigmoidal substrate dependency of enzymatic turnover enables it to act as a sensor that makes cells responsive to changes in circulating glucose levels. Its unusual kinetic properties are intrinsically linked to the enzyme's conformational dynamics.
View Article and Find Full Text PDFJ Comput Aided Mol Des
December 2024
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector-125, Noida, UP, 201313, India.
Metabolites
December 2024
Fisheries Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 611730, China.
Rice-fish farming is an ancient and enduring aquaculture model in China. This study aimed to assess the variations in digestive enzymes, antioxidant properties, glucose metabolism, and nutritional content between reared in paddy fields and ponds. Notably, the levels of amylase and trypsin in from rice paddies were considerably higher compared to those from ponds.
View Article and Find Full Text PDFAlzheimers Res Ther
December 2024
Department of Endocrinology and Metabolism, Peking University People's Hospital, 100044 No.11 Xizhimen South Street, Xicheng District, Beijing China, 100044, People's Republic of China.
Objective: To evaluate the association between anti-diabetic agents and the risks of dementia in patients with type 2 diabetes (T2D).
Methods: Literature retrieval was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov between January 1995 and October 2024.
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