Summary:

The National Cancer Institute (NCI) seeks licensees for a family of novel furoquinolinedione derivatives that inhibit tyrosyl-DNA phosphodiesterase 2 (TDP2) as cancer therapeutics.   

Description of Technology:

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is an enzyme that plays a critical role in repairing nucleic acid lesions, namely by repairing trapped DNA cleavage complexes. TDP2 repairs topoisomerase (TOP2)-mediated DNA damage induced by chemotherapeutic agents and removes endogenous TOP2-DNA cleavage complexes. Further, TDP2 deficiency potentiates the antiproliferative activity of TOP2 inhibitors. This suggest that combination therapies consisting of TDP2 and TOP2 inhibitors have a synergistic effect on tumor tissues. Therefore, TDP2 represents a promising anti-cancer pharmacological target as a monotherapy or part of a combination therapy.

The NCI investigators and their collaborators have discovered a series of novel furoquinolinedione derivatives as specific TDP2 inhibitors that could act as anti-cancer therapeutics alone and/or potentiate the pharmacological action of TOP2 inhibitors. Systematic structure-activity relationship studies were conducted and demonstrated that several furoquinolinedione derivatives had TDP2 inhibitory activity in the low micromolar or submicromolar range and act in a dose-dependent manner. Further, enzyme-based assays showed the furoquinolinedione derivatives are specific to TDP2 and showed no inhibitory activity against TDP1 and TOP1.

NCI is seeking licensees to further develop this family of compounds as anti-cancer agents.  

Potential Commercial Applications:

• Standalone cancer therapeutic
• Part of a combination cancer therapeutic with other drugs, such as TOP2 inhibitors

Competitive Advantages:

• Potential first-in-class drug (novel mechanism of action and novel composition of matter)
• Selective inhibition of TDP2
• Can be used alone or in combination with TOP2 inhibitors
• Synergistic effect to boost the efficacy of TOP2 inhibitors (decrease effective dosage, minimize side effects)
• Potential for use across many cancer types