Use of Small Molecules to Treat PARP1-deficient Cancers

Scientists at the National Human Genome Research Institute and the National Center for Advancing Translational Sciences have identified a class of small molecules synergistically working with known Poly (ADP-ribose) polymerase 1 (PARP-1)-inhibitors. These new small molecules can each effectively kill specific PARP-1 defective tumors cells and show synergy with known PARP1 inhibitors (PARP-1i) in killing tumor cells.

PARP1, a highly conserved DNA binding protein, is essential for repairing DNA damage and plays important roles in multiple DNA damage response pathways. Many cancer therapies utilize DNA-damaging agents to kill tumor cells, which often triggers DNA repair (e.g., by activating PARP1 pathways). Additionally, a variety of cancer types may also carry PARP1 mutation(s), such as glioma, breast cancer, and prostate cancer. Such mutations render the cancer cells resistant to these therapies. The key feature of these PARP-1i sensitizing molecules can be applied either as useful sensitizers in combinatorial treatment to increase the efficacy of DNA-damaging agents in cancer therapy, or selective targeting of cancer cells with specific DNA PARP-1 defects; thereby allowing for the development of new therapies.

Potential Commercial Applications:		Competitive Advantages:
Therapies for cancers associated with PARP-1 defects.		Utilizes proven small-molecule technology Specificity of mode of action may reduce potential side-effects Novel mode of action may limit market competition Combinatorial therapies of cancers with PARP-1 inhibitors

Development Stage:
In vitro data available

Inventors:

Kyungjae Myung (NHGRI)  ➽ more inventions...

Yong Choi (NHGRI)  ➽ more inventions...

Stephanie Smith (NHGRI)  ➽ more inventions...

Yongliang Zhang (NHGRI)  ➽ more inventions...

Ganesha Rai Bantukallu (NCATS)  ➽ more inventions...

Jennifer Fox (NCATS)  ➽ more inventions...

Ruili Huang (NCATS)  ➽ more inventions...

David Maloney (NCATS)  ➽ more inventions...

Menghang Xia (NCATS)  ➽ more inventions...

Matthew Boxer (NCATS)  ➽ more inventions...

Jason Rohde (NCATS)  ➽ more inventions...

Srilatha Sakamuru (NCATS)  ➽ more inventions...


Intellectual Property:
US Application No. 61/930,291
PCT Application No. PCT/US15/012493

Publications:
Papeo G, et al. PMID 23379721
Yu H, et al. PMID 22127734
Chiarugi A. PMID 22055391

Collaboration Opportunity:
The National Human Genome Research Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize small molecules to treat PARP1-deficient cancer. For collaboration opportunities, please contact Anna Solowiej, Ph.D., J.D. at solowieja@mail.nih.gov.


Licensing Contact:
Eggerton Campbell, Ph.D.
Email: eggerton.campbell@nih.gov
Phone: 301-402-1648

OTT Reference No: E-039-2014-0
Updated: Dec 16, 2015