Pyruvate Dehydrogenase Kinases as Therapeutic Targets for Cancer and Ischemic Diseases

This invention addresses two desired outcomes relating to cells exposed to ischemic or low oxygen tension by modulating the activity of a mitochondrial matrix enzyme. Tumor cells that have low oxygen tension survival mechanism may be thwarted and killed and critical cells for survival may be treated to recover from low oxygen tension enhancing the possibility of survival. The inventors have found a use of small molecules that potentiates the activity of a mitochondrial enzyme and decreases an alternative low oxygen survival mechanism ultimately inhibiting the proliferation of tumor-like cells. Conversely, increase of this enzyme's activity, could enhance the ability of this low oxygen survival pathway to rescue cells that could not adapt and otherwise die in low oxygen tension. The use of small molecules and the manipulation of this enzyme's activity can therefore be targeted to both decrease a cancer cell ischemia survival mechanism and alternatively protect tissues from ischemic damage such as occurs in stroke or myocardial infarction. Description (Set) Proposed Use (Set) 1. Mitochondrial enzyme expression vector (inhibitory effect) can be used for ischemic disease gene therapeutics. 2. Use of mitochondrial enzyme's substrate inhibitors for ischemic diseases. 3. Use of existing inhibitors of the mitochondrial enzyme for tumor therapy.

Inventor(s): Dang, Chi V.

Type of Offer: Licensing



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