Novel Mitochondrial Targeted Glioblastoma Drugs



The invention is a blood/ brain barrier permeable prodrugs which are selectively activated by an enzyme that is highly upregulated in glioma cells. The activation selectively targets the drug “warhead” to the mitochondria of glioma cells at high concentration and damages or destroys the mitochondrial DNA. Cancer cells including glioma cells contain far fewer mitochondria than normal cells but cannot survive without a minimum number of mitochondria for pyrimidine synthesis.  This requirement is the cancer cell’s “Achilles Heel” since destruction of the  mitochondria leads to rapid cancer cell death. In addition, mitochondria DNA damage does not upregulate DNA repair enzymes therefore targeting mitochondrial DNA avoids the development of drug resistance.



There are 10,000 new glioma cases in the US alone every year and the survival rate is <3% at 5 years. The most aggressive form of glioma, Glioblastoma multiforme (GBM) is also the most frequent type and no GBM patients survive for >1 year. GBM is topographically diverse and frequently cannot be completely resected. Gliomas are currently treated with a combination of surgery, radiotherapy and chemotherapy with DNA acylating agents such as temozolomide or carmustine or rarely with the topoisomerase inhibitor irinotecan. Carmustine is sometimes supplied as wafers placed into the post surgical wound. No current treatments are effective at prolonging survival for more than a few months.



  • Prodrug is blood / brain barrier permeable.
  • Prodrug is selectively activated in glioma cells by a specifically upregulated enzyme.
  • Active drug is concentrated 500 fold in the mitochondria.
  • Active drug damages mitochondrial DNA resulting in mitochondrial destruction and glioma cell death.
  • Will not trigger drug resistance since DNA repair pathways are not upregulated.
  • A variety of “warhead” drugs can be attached to the targeting moiety for glioma mitochondrial delivery.



Patent Application

PCT patent application filed.



Patent Information:
Licensing Contact
Belisa Diaz