Technology Listings


Cancer Cell Metabolism Inhibitors for Targeted Therapies

Application

Glutamate dehydrogenase (GDH1) inhibitors targeting cancer cell metabolic pathways.

Key Benefits
  • Targets tricarboxylic acid (TCA) cycle/mitochondrial metabolism utilized by several cancer cell types for cell growth and survival.
  • Reduces cell proliferation and viability in several tumor derived cell lines as well as in xenograft tumor models.
  • Limited effects on cell toxicity and proliferation rates observed in non-tumor derived cell lines or in tissues from mice treated with GDH1 inhibitors.
Market Summary

Statistics show cancer prevalence is on the rise and is projected to rise over the next decade. Advances in oncology have relied on targeted therapies that destroy the cancerous cells while resulting in minimal damage to normal cells in the patient. Often, these therapies will be applicable to only a specific cancer subtype with an inability to treat a broader array of diagnoses. However, there are some properties of cancer cells that are found in a multitude of oncological diseases, which can be targeted.

Technical Summary

Cancer cells typically have a higher metabolic demand than normal cells resulting in the utilization of increased TCA cycle/mitochondrial metabolism. Glutamate dehydrogenase (GDH1) is an enzyme that converts glutamate to the TCA cycle metabolite α-ketoglutarate. Emory researchers have identified a small molecule inhibitor of GDH1 for targeted cancer therapies. Inhibition of GDH1 decreases mitochondrial activity in tumor derived cell lines and other TCA cycle metabolites, including fumarate. A decrease in fumarate levels results in an increase of reactive oxygen species production. The observed net effect of GDH1 inhibition was a decrease in cancer cell proliferation and viability with limited to no effect on normal cell proliferation and viability.

Developmental Stage

Effectiveness has been demonstrated on cancer cell lines in vitro and xenograft tumors in vivo.

Publication: Jin et al., 2015, Cancer Cell 27, 257;270

Patent Information
App Type Country Serial No. Patent No. File Date Issued Date Expire Date
Utility(parent) United States 15/017,095 2/5/2016    
Tech ID: 15073
Published: 2/8/2016
Category
Drug Discovery

Contact
Cliff Michaels
Assistant Director
Emory University
404-727-3890
ccmicha@emory.edu

Inventor(s)
Sumin Kang
Jing Chen
Lingtao Jin

Keywords
Small Molecule
Oncology