A Rationally Designed Small Molecule That Inhibits the HIF-1α–ARNT Heterodimer from Binding to DNA in Vivo

Sci. STKE, 17 May 2005
Vol. 2005, Issue 284, p. pe23
DOI: 10.1126/stke.2842005pe23

A Rationally Designed Small Molecule That Inhibits the HIF-1α–ARNT Heterodimer from Binding to DNA in Vivo

  1. Charles Vinson
  1. Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  1. *Contact information. E-mail: Vinsonc{at}mail.nih.gov

Abstract

Modern drug development is focused on two steps: the identification of new molecular targets and the development of drugs that affect these targets. A molecular target can be an enzymatic activity or a macromolecular interface that is important in a disease pathway. Current drugs on the market are biased toward targeting cell surface receptors and intracellular enzymatic activities. However, macromolecular interfaces can also serve as potential molecular targets. A recent paper from Kaelin and Dervan's groups examined an underused molecular target—transcription factor DNA binding. To specifically disrupt transcriptional activation, they used a rationally designed small molecule that binds specifically in the minor groove of a DNA sequence that in vivo is bound by a bHLH heterodimer transcription factor.

Citation:

C. Vinson, A Rationally Designed Small Molecule That Inhibits the HIF-1α–ARNT Heterodimer from Binding to DNA in Vivo. Sci. STKE 2005, pe23 (2005).
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