Chloro-oxime derivatives as novel small molecule chaperone amplifiers

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 (EC50

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-06, Vol.19 (11), p.3128-3135
Main Authors: Zhou, Yuefen, Vu, Khang, Chen, Yongsheng, Pham, John, Brady, Thomas, Liu, Gang, Chen, Jinhua, Nam, Joonwoo, Murali Mohan Reddy, P.S., Au, Qingyan, Yoon, Il Sang, Tremblay, Marie-Helene, Yip, Gary, Cher, Charmian, Zhang, Bin, Barber, Jack R., Ng, Shi Chung
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Line, Tumor
Chloro-oxime derivatives
Cytoprotection
DNA-Binding Proteins - metabolism
ER stress
Heat Shock Transcription Factors
HSF1, heat shock proteins (HSPs)
Humans
Medical sciences
MG-132 stress
Molecular Chaperones - chemistry
Molecular Chaperones - metabolism
Neurodegenerative diseases
Neuropharmacology
Neuroprotective agent
Oximes - chemical synthesis
Oximes - chemistry
Oximes - pharmacology
Pharmacology. Drug treatments
PolyQ stress
Protein misfolding
Small molecule chaperone amplifiers
Stress granule
Structure-Activity Relationship
Transcription Factors - metabolism
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Summary: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 (EC50
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.03.011