title: Structure-activity analysis and cell-based optimization of human galactokinase inhibitors.
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.
authors: Division of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT 84132, U.S.A.
authors: Si
authors: S
authors: Odejinmi
authors: Rg
authors: R
authors: Rascon
authors: M
authors: M
authors: Tang
authors: H
authors: H
authors: Vankayalapati
authors: K
authors: K
authors: Lai