Glycolysis Inhibitors as Potential Cancer Therapeutics

Application

A new potential anti-cancer agent that inhibits the glycolytic enzyme PGAM1 and thereby tumor growth.

Key Benefits

Targets tumor metabolism by inhibiting glycolytic enzyme and turning off tumor metabolism.
Inhibition of glycolytic enzyme (PGAM1) by these inhibitors leads to significant reduction in tumor growth.

Market Summary

There is a 1 in 3 chance each American will develop a cancer over his or her lifetime, and survival rates vary widely, from as high as 99% in breast cancer to as low as 5% in metastasized lung cancer. Even effective cancer therapies have extensive side effects, and new treatments are in high demand.

Technical Summary

Cells generate the energy they need to function via glycolysis with cancer cells undergoing rates of glycolysis 200 times greater than normal cells. Glycolytic inhibitors may therefore treat cancer by slowing these abnormal rates of tumor cell glycolysis and "starving" the tumor cells. Emory inventors have designed a novel group of glycolytic inhibitors that down-regulate activity of the enzyme PGAM1, which catalyzes the breakdown of glucose into useable energy. In addition to glycolysis, PGAM1 also regulates RNA/DNA biosynthesis through unique crosstalk mediated by its metabolic product. Thus, these compounds inhibit PGAM1 activity in leukemia and lung cancer cell lines, and suppress tumor growth in rodent models of cancer to a much greater extent than other glycolytic inhibitors by shutting down both glycolysis and biosynthesis. Cancer cells that exist in low-oxygen conditions or that have dysfunctional mitochondria are often resistant to conventional anti-cancer therapies. Due in part to this resistance, glycolytic inhibitors appear to be particularly effective against these types of cancer cells.

Developmental Stage

Effectiveness of inhibitors have been determined in both cell-based assays and rodent models.

Publication: Hitosugi, T. et al. (2012). Cancer Cell, 22(5), 585-600.

Patent Information

App Type	Country	Serial No.	Patent No.	File Date	Issued Date	Patent Status
Nationalized PCT - United States	United States	14/349,550	9,884,815	4/3/2014	2/6/2018	Issued
Divisional	United States	15/847,670	10,464,890	12/19/2017	11/5/2019	Issued