Abstract
Chloro-oxime derivatives were investigated as novel small molecule chaperone amplifiers. Lead optimization led to the discovery of compounds that displayed potent HSF1 activation activity, significant cytoprotection in MG-132 stress, ER stress and PolyQ stress cell models (EC(50)<10 microM).
MeSH terms
-
Cell Line, Tumor
-
Cytoprotection
-
DNA-Binding Proteins / metabolism
-
Heat Shock Transcription Factors
-
Humans
-
Molecular Chaperones / chemistry*
-
Molecular Chaperones / metabolism
-
Oximes / chemical synthesis
-
Oximes / chemistry*
-
Oximes / pharmacology
-
Structure-Activity Relationship
-
Transcription Factors / metabolism
Substances
-
DNA-Binding Proteins
-
HSF1 protein, human
-
Heat Shock Transcription Factors
-
Molecular Chaperones
-
Oximes
-
Transcription Factors