Unmet Need: Targeted cancer therapies against DNA repair enzymes have successfully been implemented in cancer treatments but now suffer from the development of drug resistance. There is a need for additional DNA repair enzyme targets to overcome current resistance issues.
Technical Details: Johns Hopkins researchers have identified an inhibitor of DNA repair enzyme DNA polymerase beta for therapeutic cancer treatment. DNA polymerase beta is overexpressed in a variety of cancer cells, and functions to repair DNA damage through its lyase activity in order to prolong cancer cell survival. Using a library of small molecules, researchers performed an extensive screen of possible DNA polymerase beta inhibitors and identified an irreversible inhibitor candidate of its lyase activity. This candidate was shown in vitro to limit DNA polymerase beta activity in prostate cancer cell lysates. Multiple DNA repair enzymes utilize lyase activity to perform their functions, allowing for broad application of the inhibitor disclosed in the targeting of lyase containing DNA repair enzymes. Finally, the candidate also demonstrates synergistic inhibition with DNA damaging agent methyl methanesulfonate (MMS). This compound can be administered to cancer patients as a novel therapeutic treatment option.
Value Proposition:
· Novel irreversible inhibitor compound of DNA repair enzyme DNA polymerase beta
· Broad inhibition potential for additional enzymes upregulated in cancer cells through targeting lyase activity
· Therapeutic method of use to treat cancer patients synergistically with DNA damaging chemotherapeutic agents
Looking for Partners to: Develop & commercialize the technology as an irreversible inhibitor of DNA repair enzyme activity to treat cancer.
Stage of Development: Pre-Clinical
Data Availability: In vitro
Inventors: Arian Dumitru, Marc M. Greenberg, Mohammad Hedayati, Theodore L. DeWeese
