Structure-activity analysis and cell-based optimization of human galactokinase inhibitors.

Basic Information

ID: ALA2016474

Journal: ACS Med Chem Lett

Title: Structure-activity analysis and cell-based optimization of human galactokinase inhibitors.

Authors: Odejinmi S, Rascon R, Tang M, Vankayalapati H, Lai K.

Abstract: Classic Galactosemia is a rare human disease associated with the accumulation of toxic level of galactose-1-phosphate (gal-1P) caused by the inherited deficiency of galactose-1-phosphate uridyltransferase (GALT) activity. To reduce the toxic level of gal-1P in the patients, we have identified, via high-throughput screening, over 200 small molecule GALK inhibitors. We selected a 4-oxo-3,4-dihydro-2H-1,3-thiazine-5-carbonitrile scaffold for further structure-activity relationships characterization, lead optimization with regards to potency and efficacy to reduce gal-1P accumulation in patient cells.

CiteXplore: 22125663

DOI: 10.1021/ml200131j

Patent ID: