Small Molecule Activators of Human Pyruvate Kinase for Treatment of Cancer and Enzyme-Deficient Hemolytic Anemia

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 adult cells only PK isoforms R, L, or M1 are active, in all tumors only PK-M2 is active. Therefore, PK-M2 activation would affect only tumor cells, and small-molecule PK-M2 activators are not expected to be toxic to healthy cells.

In addition, in patients with PK-R deficiency the buildup of metabolic intermediates in red blood cells ultimately leads to the loss of water from the cells and cell death. Small-molecule induced activation of PK-R in PK-deficient red blood cells may enhance vitality of these cells and decrease or eliminate enzyme-deficient hemolytic anemia in a patient.

Potential Commercial Applications: Competitive Advantages:
  • Therapeutic for cancer
  • Therapeutic for enzyme-deficient hemolytic anemia

Development Stage:
Early stage


Craig Thomas (NCATS)  ➽ more inventions...

Intellectual Property:
U.S. Pat: 8,841,305 issued 2014-09-23
U.S. Pat: 8,937,067 issued 2015-01-20
U.S. Pat: 9,707,230 issued 2017-07-18
U.S. Pat: 9,290,512 issued 2016-03-22
US Application No. 15/076,258
US Application No. 14/576,333

In preparation

Collaboration Opportunity:

The NIH Chemical Genomics Center is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize appropriate lead compounds described in U.S. Provisional Application No. 61/199,763. Please contact Dr. Craig J. Thomas via e-mail ( for more information.

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

OTT Reference No: E-326-2008-0
Updated: May 5, 2009