Potent inhibitors of Huntingtin protein aggregation in a cell-based assay.
A quinazoline that decreases polyglutamine aggregate burden in a cell-based assay was identified from a high-throughput screen of a chemical-compound library, provided by the NIH Molecular Libraries Small Molecule Repository (MLSMR). A structure and activity study yielded leads with submicromolar potency.
Rinderspacher
Alison
A
Division of Experimental Therapeutics, Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Cremona
Maria Laura
ML
Liu
Yidong
Y
Deng
Shi-Xian
SX
Xie
Yuli
Y
Gong
Gangli
G
Aulner
Nathalie
N
Többen
Udo
U
Myers
Katherine
K
Chung
Caty
C
Andersen
Monique
M
Vidović
Dusica
D
Schürer
Stephan
S
Brandén
Lars
L
Yamamoto
Ai
A
Landry
Donald W
DW
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D000071058:Huntingtin Protein; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000737:chemistry; D011799:Quinazolines / Q000737:chemistry*; D013329:Structure-Activity Relationship
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D011799:Quinazolines; C097188:polyglutamine