title: Activators of PKM2 in cancer metabolism.
abstract: Pyruvate kinase converts phosphoenolpyruvate to pyruvate, catalyzing the rate-limiting step of glycolysis. The M1 isoenzyme of pyruvate kinase (PKM1) is found in adult tissues; whereas, PKM2 is a splicesome variant found in embryonic and cancer cells. PKM2 expression in malignant cells is a result of the tumor microenvironment and is responsible for maintaining a glycolytic phenotype. PKM2 has other nonmetabolic functions in malignant cells, including transcriptional coactivation and protein kinase activity. PKM2 activators have antitumor properties by inducing tetramerization of two PKM2 dimers causing PKM2 to function like PKM1. Restoring PKM2 to PKM1-like levels of activity causes reversal of the Warburg effect in cancer cells. PKM2 activators have therapeutic potential in the treatment of cancer and other metabolic diseases.
authors: Tolero Pharmaceuticals, Inc., 2975 W Executive Parkway, Suite 320, Lehi, UT 84043, USA.
authors: Steven L
authors: SL
authors: Warner
authors: Kent J
authors: KJ
authors: Carpenter
authors: David J
authors: DJ
authors: Bearss
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D008565:Membrane Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013963:Thyroid Hormones / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D008565:Membrane Proteins; D054852:Small Molecule Libraries; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins