Development of LC/MS/MS, high-throughput enzymatic and cellular assays for the characterization of compounds that inhibit kynurenine monooxygenase (KMO).
J Biomol Screen
; 18(8): 879-89, 2013 Sep.
Article
in En
| MEDLINE
| ID: mdl-23690293
ABSTRACT
Kynurenine monooxygenase (KMO) catalyzes the conversion of kynurenine to 3-hydroxykynurenine. Modulation of KMO activity has been implicated in several neurodegenerative diseases, including Huntington disease. Our goal is to develop potent and selective small-molecule KMO inhibitors with suitable pharmacokinetic characteristics for in vivo proof-of-concept studies and subsequent clinical development. We developed a comprehensive panel of biochemical and cell-based assays that use liquid chromatography/tandem mass spectrometry to quantify unlabeled kynurenine and 3-hydroxykynurenine. We describe assays to measure KMO inhibition in cell and tissue extracts, as well as cellular assays including heterologous cell lines and primary rat microglia and human peripheral blood mononuclear cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Kynurenine 3-Monooxygenase
/
Enzyme Assays
Limits:
Animals
/
Humans
Language:
En
Journal:
J Biomol Screen
Journal subject:
BIOLOGIA MOLECULAR
Year:
2013
Document type:
Article
Affiliation country: