New Target Identified for Cancer Therapy and Its Inhibitor

A major challenge in developing efficacious cancer therapies is the identification of target protein. Once a target is identified drugs can be developed and evaluated for their ability to inhibit the target. Recently through a collaboration with Scripps Research Institute and Purdue University, DNA polymerase epsilon subunit 3 (POLE3) has been identified as a target for cancer therapeutics. POLE3 combines with other enzymes to form a complex involved in DNA replication which occurs more frequently in cancerous cells than normal cells.

Researchers at Purdue University have developed the first reported inhibitors of POLE3. The group of compounds that have been identified as POLE3 inhibitors are synthetic derivatives of beshanzuenone, a natural molecule from the Chinese fir tree. Beshanzuenone was previously reported to have activity against PTP1B, a target for diabetes II and obesity. In addition to the POLE3 inhibitors, new synthetic derivatives of beshanzuenone were also identified to have potent activity against SHP2 via a novel mode of action. SHP2 is a validated oncogenic target for a variety of human cancers.

Total Synthesis, Biological Evaluation, and Target Identification of Rare Abies Sesquiterpenoids

J. Am. Chem. Soc., 2018, 140 (50), pp 17465–17473

DOI: 10.1021/jacs.8b07652

Advantages:

-New target for cancer therapy

Potential Applications:

-Development of new therapies for cancer

-Tool compound

TRL: 2

Intellectual Property:

Keywords: cancer therapeutics, POLE3 inhibitors, SHP2 inhibitors, beshanzuenone derivatives, DNA polymerase epsilon subunit 3, oncogenic target, cancer therapy, targeted therapy, Chinese fir tree, tool compound