Pyruvate Kinase M2 Activators for the Treatment of Cancer

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.

Potential Commercial Applications: Competitive Advantages:
  • Therapeutic developments for various cancers
  • Diagnostic assays for various cancers
  • Regulation of embryonic stem cell proliferation
  • Small molecule (series of analogs can be derived in search of improved performance)
  • Target a select group of cells (Cancerous cells)

Development Stage:
  • Early-stage
  • In vitro data available


Matthew Boxer (NCATS)  ➽ more inventions...

Douglas Auld (NCATS)  ➽ more inventions...

Craig Thomas (NCATS)  ➽ more inventions...

Min Shen (NCATS)  ➽ more inventions...

Intellectual Property:
PCT Pat: 9,708,267 issued 2017-07-18
US Application No. 13/643,594 filed on 2012-10-26
US Application No. 61/329,158 filed on 2010-04-29
US Application No. 14/643,107 filed on 2015-03-10

Jiang JK, et al. PMID 20451379
Boxer MB, et al. PMID 20017496

Collaboration Opportunity:

The National Center for Advancing Translational Sciences is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these pyruvate kinase M2 activators. Please contact Dr. Matthew Boxer at for more information.

Licensing Contact:
Suryanarayana Vepa, Ph.D.
Phone: 301-827-7181

OTT Reference No: E-120-2010-0
Updated: Mar 12, 2015