Karen Atkinson

TL;DR: 19 is identified as a potent glucokinase activator with a greater than 50-fold liver-to-pancreas ratio of tissue distribution in rodent and non-rodent species, leading to its selection as a clinical development candidate for treating type 2 diabetes.

TL;DR: The results showed that the relay method produced excellent predictions of human in vivo clearance, and the difference between in vitro and in vivo intrinsic clearance was within 2-fold for most compounds, which is similar to the standard prediction accuracy for moderate to high clearance compounds using hepatocytes.

TL;DR: The multicomponent construct described here represents a highly efficient delivery vehicle to hepatocytes and exhibits increased ASGPR-directed hepatocellular uptake and prolonged retention compared to a similar GalNAc derived trimer conjugate.

TL;DR: This work has investigated a series of substituted 2-methylbenzofurans as “partial activators” of the glucokinase enzyme leading to the identification of N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)-carbamoyl)benz ofuran-4-yloxy)pyrimidine- 2-carboxamide as an early development candidate.

TL;DR: In vitro-in vivo correlation (IVIVC) of intrinsic clearance in preclinical species of rat and dog was established using the hepatocyte relay method to support high-confidence prediction of human pharmacokinetics for low-clearance compounds as discussed by the authors.