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.
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Lori W
LW
Lee
Christopher E C
CE
Taylor
Jean-Paul
JP
Desaulniers
Manchao
M
Zhang
Jonas W
JW
Højfeldt
Quintin
Q
Pan
Anna K
AK
Mapp
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