Invention Spotlight: Patent Application Issued for Indole Molecules and Use Thereof in the Inhibition of DNA Polymerases

Congratulations to inventors Robert Eoff, Narsimha Penttala, and Peter Crooks on the issuing of U.S. Patent Application No. 12,685,733, titled Indole Molecules and Use Thereof in the Inhibition of DNA Polymerases. The technology describes a new class of indole-derived compounds designed to inhibit DNA polymerases involved in cancer cells’ ability to tolerate DNA damage and resist treatment.

Many cancer therapies, including radiation and chemotherapy, work by damaging tumor-cell DNA. Cancer cells can develop mechanisms that allow them to continue replicating despite this damage, reducing the effectiveness of treatment and contributing to tumor recurrence.

One mechanism involves translesion synthesis (TLS) DNA polymerases, which allow cells to replicate past damaged sections of DNA. While this process can help cells survive, it can also increase mutations and contribute to treatment resistance. This is particularly relevant in cancers such as glioblastoma, where resistance to the DNA-damaging chemotherapy temozolomide remains a major therapeutic challenge.

This patented technology introduces indole-derived molecules that inhibit these DNA polymerases, including compounds designed to selectively target DNA polymerase kappa (Pol κ). By interfering with this DNA damage-tolerance pathway, the compounds are intended to make cancer cells more vulnerable to existing genotoxic therapies.

Preclinical studies described in the application show that the lead compound IAG-10 selectively inhibits Pol κ and can sensitize glioblastoma-derived cells to temozolomide. The studies also demonstrate reduced glioma spheroid growth and increased sensitivity of glioblastoma stem cells when Pol κ inhibition is combined with temozolomide.

This approach could provide a new strategy for addressing treatment-resistant tumors by targeting the cellular mechanisms that allow cancer cells to survive DNA-damaging therapy. The technology also describes the potential use of these compounds alongside existing cancer treatments, including chemotherapy and other genotoxic agents.

BioVentures congratulates Dr. Eoff, Dr. Penttala, and Dr. Crooks on the issued patent application and recognizes their work in advancing new approaches to overcoming therapeutic resistance in cancer.