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New Energy Restriction-Mimetic Agents for Cancer Treatment

Life Sciences
Therapeutics
Drugs / Pharmaceuticals
College
College of Pharmacy
Researchers
Chen, Ching-Shih
Licensing Manager
Paschall, Christopher
614-688-2727
paschall.12@osu.edu

T2010-001 Development of thiazolidinedione (TZD), OSU-CG12, as a novel energy restriction-mimetic agent for cancer therapy and chemo-prevention.

The Need

Cancer cells shift cellular metabolism to aerobic glycolysis to gain growth advantages in microenvironments, which has raised interest in therapies that exploit the response of malignant versus normal cells to glycolytic inhibition. Chronic energy restriction is difficult to implement as a chemo-preventive strategy, but energy restriction-mimetic agents (ERMAs), such as 2-deoxyglucose and resveratrol, pose alternative solutions because these compounds inhibit glucose metabolism and uptake. However, the therapeutic applications of these agents are restricted by relatively weak in vitro potencies. More potent ERMAs must be developed to improve the therapeutic effects of these compounds.

The Technology

Dr. Ching-Shih Chen, a researcher at The Ohio State University, has described thiazolidinediones (TZDs) as a novel scaffold for the development of ERMAs. In addition, Dr. Chen developed a proof-of-concept TZD, called OSU-CG12, which demonstrated greater energy restriction effects compared to 2-deoxyglucose and resveratrol. A study of OSU-CG12 demonstrated that the compound induced key starvation-associated responses, such as transient Sirt 1 induction, AMPK activation, and ER stress. This data provides considerable support for use of TZDs in treatment of a number of spontaneous or chemical-induced tumor conditions. The proof-of-concept for this invention has been established in vitro and is funded by a National Cancer Institute grant.

Commercial Applications

  • Oncological therapeutics
  • Pharmaceuticals

Benefits/Advantages

  • Able to be administered orally (orally bioavailable)
  • Greater potency than commonly used ERMAs
  • Inhibits cancer glucose metabolism
  • Shows cancer cell anti-proliferative effects from increases in natural cell death due to apoptosis and autophagy
  • The IC-50 of the lead compound (OSU CG12) has been found to be 5-5.7 uM