Pyruvate Kinase M2 (PKM2) is a key enzyme that gates the abnormal metabolism within cancer cells. Pyruvate Kinase M2 (PKM2) is one of four pyruvate kinase isoenzymes, that catalyze the last step in glycolysis. PKM2 is expressed in cells with a high rate of nucleic acid synthesis, mainly proliferating cells such as embryonic cells, adult stem cells, and cancer tumor cells.
PKM2 undergoes a transformation from an energy efficient tetrametic form to an ‘energy inefficient’ dimer form (which leads to the accumulation of building blocks necessary for biosynthesis). The main effector that balances the Dimer-Tetramer ratio of PKM2 in tissues is fructose 1,6-bisphosphate (FBP), a glycolysis intermediate product upstream of PKM2. PKM2 is a key mediator of the Warburg effect in cancer cells leading to lower energy production and an abundance of building blocks for tumor replication and growth.
A therapeutic drug that will 'renormalize’ the metabolism within cancer cells by stabilizing the ‘energy efficient’ form of PKM2 in tumor cells, will limit the availability of building blocks necessary for biosynthesis, thus reducing the ability of these cells to grow and proliferate.
Dynamix is at the leading edge of the emerging field of cancer metabolism, and our PKM2 program is among the most advanced programs in this field.
Dynamix is developing several series of small-molecule PKM2 activators (DNX-03000) which target two regions of the PKM2 tetramer. Extensive data, both in vitro and in vivo, validates the utility of these novel agents as anti-cancer therapeutics, both as monotherapy or in combination with other agents. This PKM2 program is currently in preclinical development. Some of the data was presented in a AACR 2011 Poster.
For more information please contact Dynamix.