Inhibition of ErbB2(Her2) expression with small molecule transcription factor mimics.
Small molecules that mimic the transcriptional activation domain of eukaryotic transcriptional activators have the potential to serve as effective inhibitors of transcriptional processes. Here we show that one class of transcriptional activation domain mimics, amphipathic isoxazolidines, can be converted into inhibitors of gene expression mediated by the transcriptional activator ESX through small structural modifications. Addition of the small molecules leads to decreased expression of the cell surface growth receptor ErbB2(Her2) in ErbB2-positive cancer cells and, correspondingly, decreased proliferation.
Lee
Lori W
LW
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Taylor
Christopher E C
CE
Desaulniers
Jean-Paul
JP
Zhang
Manchao
M
Højfeldt
Jonas W
JW
Pan
Quintin
Q
Mapp
Anna K
AK
D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D007555:Isoxazoles; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors