Methods and compositions for modulating oxygen homeostasis for therapeutic application

The hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays a pivotal role in cellular adaptation to oxygen availability. HIF-1alpha protein is a subunit of HIF-1. Although the gene for HIF-1alpha is constitutively expressed, it is an extremely short-lived protein under normoxic conditions and is targeted for destruction via the proteosome pathway by an E3 ubiquitin ligase involving the VHL protein.

The invention relates to the discovery that mutations or deletions of Leu574 result in a more stable and more active form of HIF-1alpha. Therefore, the invention relates to methods and compositions for modulating oxygen homeostasis for therapeutic application. In one aspect, the inventors contemplate the use of a more stable form of HIF-1alpha protein for therapeutic angiogenesis purposes such as may be useful in ischemic vascular disease. In another aspect, the inventors contemplate the use of this particular site in a screen for targeted drugs that modulates HIF-1alpha activity. The inventors also suggest that Leu574 could be used for developing drugs targeted to HIF hydroxylase binding, thereby altering HIF-1alpha stability.

Early Stage

U.S. Patent No. 7,193,053 issued 20 Mar 2007 (HHS Reference No. E-281-2002/0-US-02)

Inventor:
L. Eric Huang (NCI)

Licensees Sought:
This technology is available for licensing on an exclusive or a non-exclusive basis.