Inhibition of ErbB2(Her2) expression with small molecule transcription factor mimics.

Bioorg Med Chem Lett 2009 Nov 1;19(21):6233-6. Epub 2009 Sep 1.

Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2009.08.090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782467PMC
November 2009

Publication Analysis

Top Keywords

transcriptional activation
8
small molecules
8
activation domain
8
transcriptional
5
transcriptional processes
4
erbb2her2 erbb2-positive
4
esx small
4
processes class
4
erbb2-positive cancer
4
inhibitors transcriptional
4
serve effective
4
leads decreased
4
effective inhibitors
4
potential serve
4
small structural
4
class transcriptional
4
inhibitors gene
4
cell surface
4
gene expression
4
surface growth
4

Similar Publications