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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.

SUBMITTER: Odejinmi S

PROVIDER: S-EPMC3224021 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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

Odejinmi Si S Rascon Rg R Tang M M Vankayalapati H H Lai K K

ACS medicinal chemistry letters 20110901 9

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 ...[more]

PMID: 22125663

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