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Pyruvate kinase modulators as a therapy target: an updated patent review 2018-2023
Sevki Adem1, Azhar Rasul2, Saba Riaz2
1Faculty of Science, Chemistry Department, Cankiri Karatekin University, Cankiri, Turkey.
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.
Insights
Cancer cells utilize pyruvate kinase M2 (PKM2) for energy. This review explores recent patents on PKM2 activators and inhibitors, highlighting their potential in cancer treatment by modulating cell proliferation.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Cancer cells exhibit altered metabolism, favoring glycolysis for energy.
- Pyruvate kinase M2 (PKM2) is a key regulator in cancer metabolic reprogramming and is overexpressed in various cancers.
- PKM2 dimerization generates precursors essential for cancer cell growth and proliferation.
Purpose of the Study:
- To review recent patents (2018-2023) on PKM2 activators and inhibitors.
- To analyze the biological and synthesis properties of these compounds.
- To identify novel therapeutic strategies targeting PKM2 in cancer.
Main Methods:
- Advanced search of the European Patent Office (EPO) database.
- Literature search using PubMed, Google Scholar, and Elsevier.
- Classification of PKM2 modulators based on chemical structures.
Main Results:
- PKM2 activators and inhibitors are diverse, including pyrazole, phenol, and benzoxazine derivatives.
- These compounds demonstrate potential in treating various cancer types.
- Activating PKM2 can reduce cell proliferation by limiting essential biomolecules for cell formation.
Conclusions:
- PKM2 plays a critical role in cancer metabolism and proliferation.
- Developing potent and selective PKM2 activators and inhibitors is crucial for effective cancer therapy.
- Recent patents reveal promising chemical scaffolds for PKM2-targeted drug discovery.
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