Protein domain mimetics as in vivo modulators of hypoxia-inducible factor signaling.

ABSTRACT: Selective blockade of gene expression by designed small molecules is a fundamental challenge at the interface of chemistry, biology, and medicine. Transcription factors have been among the most elusive targets in genetics and drug discovery, but the fields of chemical biology and genetics have evolved to a point where this task can be addressed. Herein we report the design, synthesis, and in vivo efficacy evaluation of a protein domain mimetic targeting the interaction of the p300/CBP coactivator with the transcription factor hypoxia-inducible factor-1α. Our results indicate that disrupting this interaction results in a rapid down-regulation of hypoxia-inducible genes critical for cancer progression. The observed effects were compound-specific and dose-dependent. Gene expression profiling

SUBMITTER: Kushal S 

PROVIDER: S-EPMC3785738 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature