Indole molecules and use thereof in the inhibition of DNA polymerases

Compositions and methods for the inhibition of DNA polymerases. The methods and compositions as described herein are useful in the treatment of cancer. In particular, the present disclosure provides compositions comprising one or more of indole-derived compounds useful in treatment of cancers, including those which are resistant to genotoxic therapies.
Indole molecules and use thereof in the inhibition of DNA polymerases

KEY BENEFITS

  • Cytotoxic Effect
  • Synergic effects with current therapies

Glioblastomas are one of the most aggressive and hard-to-treat cancers, with a very low survival rate. Studies have shown that an increase in hpol κ is directly correlated to advanced cancer stages and lower survival time. Inventors have tested indole molecules as an inhibitor of DNA polymerases. These indole derivatives also work synergically to increase the potency of temozolomide, the standard of care for glioblastomas. Inhibitors of EndoG endonuclease would also be useful for increasing resistance of normal tissues surrounding tumors when DNA-damaging and cell death-inducing chemotherapeutics are used to promote cell death in cancer cells. Using helicase inhibitors for the development of antiviral agents directly targeting the viral life cycle seems to be the most promising therapeutic strategy against the spread of infection, giving these compounds a promising future in therapeutics.

ABSTRACT

The present disclosure provides compositions and methods for the inhibition of DNA polymerases. The methods and compositions described herein are useful in treating cancer. In particular, the present disclosure provides compositions comprising one or more indole-derived compounds useful in the treatment of cancers, including those which are resistant to genotoxic therapies.

INVENTORS

PATENT INFORMATION


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