Pyruvate kinase activators as a therapy target: a patent review 2011-2017

ABSTRACT

Introduction: It is well known that cancer cells have an altered metabolism both to meet the energy needs and to provide initial molecules for the synthesis of macromolecules. To cope with the new metabolic state, different forms of certain enzymes are expressed in extreme amounts. These enzymes are seen as very attractive targets to deal with cancer. Pyruvate kinases isoenzyme M2 (PKM2) is a key enzyme that determines whether glucose is used for energy or synthesis of biosynthetic molecules. The dimeric form of PKM2 main form in several cancer cells serves the formation of synthetic precursors required for the cell growth and proliferation from glycolytic intermediates.

Areas covered: This article reviews appropriate publications on PKM2 activators from the points of view of synthesis and biological activities between 2011–2017. Herein, based on the chemical structure, PKM2 activators are classified into sulfonamide, phenolic, carboxamide and pyridopyrimidinone derivatives.

Expert opinion: PKM2 activation inhibits cell growth and proliferation by decreasing a number of biomolecules required for cell building. Therefore; PKM2 activators are considered as an ideal drug for or the treatment of many cancer pathogens. It is necessary to discover new, more active and selective compounds for PKM2 activation.

KEYWORDS:

• Pyruvate kinases isoenzyme M2
• cancer
• activator
• phenolic compound
• sulfonamide
• carboxamide

Article highlights

• PKM2 is a key enzyme in glycolytic pathway control at the tumor cell metabolism.

• The activation of the PKM2 decreases the growth and the proliferation of cancer cells.

• Based on the chemical structure and activation effects reported in the literature, PKM2 activators are classified into sulfonamide, phenolic, carboxamide and pyridopyrimidinone derivatives.

• In the near future, PKM2 activators will be an appropriate medical agent for clinical studies on cancer treatment.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper has not been funded.