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Introduction: Cancer cells adopt a glycolytic phenotype to fulfill their energy needs in unfavorable conditions. In metabolic rewiring, cancer cells upregulate the expression of glycolytic pathway regulators including glucose transporter 1, hexokinase 2, and PKM2 (pyruvate kinase) into its M2 splice form. Among these regulators, PKM2 plays a major role in metabolic reprogramming and is overexpressed in various diseases, including cancer. Dimerization of PKM2 causes the generation of synthetic precursors from glycolytic intermediates, which are essential for cellular growth and cancer cell proliferation., Covered Areas: This article is focused on examining recent patents (2018-2023) on PKM2 activators, inhibitors and their biological and synthesis properties by using the advanced search service of the European Patent Office (EPO). Moreover, other databases including PubMed, Google Scholar and Elsevier were also examined for scientific data. On basis of their chemical structures, PKM2 activators and inhibitors are classified into pyrazole, pyrolidine-pyrazole, phenol, benzoxazine, isoselenazolo-pyridinium, phthalazine, and propiolylamide derivatives., Expert Opinion: Activating PKM2 reduces proliferation and development of cells by reducing the quantity of biomolecules needed for cell formation. PKM2 activators and inhibitors are highly effective in treating many cancer pathogens. It is important to find new, more potent and selective molecules for PKM2 activation and inhibition.

Aldose reductase (AR) is the first enzyme of the polyol pathway that has physiological importance under hyperglycaemic conditions. The article has been focussed on AR enzyme inhibition by selected compounds. For this purpose, the in vitro inhibitory effects of various compounds on commercially available recombinant human AR (rAR) enzyme activity were investigated. The IC 50 values of compounds on rAR inhibition effect were found for 6-hydroxy flavone, syringic acid, diosmetin, 6-fluoroflavone, 7-hydroxy-4'-nitroisoflavone, myricetin as 2.05, 2.97, 15.75, 16.1, 49.5, and 63 µM, respectively. 6-Hydroxy flavone and syringic acid competitively inhibited rAR with respect to the NADPH with K i values 0.509 ± 0.036 and 0.842 ± 0.012 µM. In addition, docking studies were performed to evaluate the potential enzyme binding positions of the compounds. Our in vitro and in silico results indicated that the 6-hydroxy flavone may be a good lead compound in the development of AR inhibitors to prevent diabetic complications.

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.