Technology Bundle ID
TAB-2202

Pyruvate Kinase M2 Activators for the Treatment of Cancer

Applications
Therapeutics
Linked ID
E-120-2010-0
Lead Inventors
Matthew Boxer (NCATS)
Co-Inventors
Craig Thomas (NCATS)
Douglas Auld (NCATS)
Min Shen (NCATS)
Development Status
  • Early-stage
  • In vitro data available
Therapeutic Areas
Oncology
ICs
NCATS
NIH investigators have discovered a series of small compounds with the potential to treat a variety of cancers as well as hemolytic anemia. Contrary to most cancer medications, these molecules can be non-toxic to normal cells because they target a protein specific to the metabolic pathways in tumors, thus representing a significant clinical advantage over less-specific chemotherapeutics.

The invention described here is a series of small molecules that activate pyruvate kinase (PK) isoform M2. PK-M2 is a critical metabolic enzyme that is affected in all forms of cancer. Inactivation of PK-M2 leads to a buildup of metabolic intermediates inside the cell. Tumor cells require a buildup of metabolic intermediates in order to undergo rapid cell growth and proliferation. Hence, activation of PK-M2 in tumor cells may prevent the buildup of metabolic intermediates and thereby stall tumor cell proliferation or destroy the tumor cells. Further, while in normal post-embryonic cells only PK isoforms R, L, or M1 are active, in all tumors only PK-M2 is active. So, PK-M2 activation would affect only tumor cells, and small-molecule PK-M2 activators may not be toxic to healthy cells.

This invention discloses the use of two new small molecule pharmacophores that can activate PKM2 through the allosteric site: 3-oxo-3,4-dihydro-2H-benzo [b] [1,4] oxazine-7-sulfonamides, and 2-oxo-1,2,3,4-tetrahydroquinoline-6-sulfonamides.
Commercial Applications
  • Therapeutic developments for various cancers
  • Diagnostic assays for various cancers
  • Regulation of embryonic stem cell proliferation
Competitive Advantages
  • Small molecule (series of analogs can be derived in search of improved performance)
  • Target a select group of cells (Cancerous cells)

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