Shenping Liu

TL;DR: The first crystal structure of a herpesvirus polymerase is presented, the Herpes Simplex Virus type 1 DNA polymerase, at 2.7 Å resolution and a novel inhibition mechanism is proposed in which a representative of a series of non-nucleosidic viral polymerase inhibitors, the 4-oxo-dihydroquinolines, binds at the polymerase active site interacting non-covalently with both the polymer enzyme and the DNA duplex.

TL;DR: This work describes the first rational targeting of tyrosine residues in a protein binding site by small-molecule covalent probes, illustrating the utility of sulfonyl fluoride probes designed to react with specific tyrosines of a protein and augments the chemical biology toolkit by these probes uses in target validation and molecular pharmacology.

TL;DR: The structural results are supported by biophysical studies with IL-17A variants produced by site-directed mutagenesis and the selection of a different receptor polypeptide to complete the cytokine-receptor complex.

TL;DR: Subsequent evaluation against the rat DAAO enzyme revealed a divergent SAR versus the human enzyme and may explain the high exposures of drug necessary to achieve significant changes in rat or mouse cerebellum D-serine.

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.