An Update on Patents Covering Agents That Interfere with the Cancer Glycolytic Cascade. (9th October 2018)

• Record Type: Journal Article
• Authors: Fortunato, Serena; Bononi, Giulia; Granchi, Carlotta; Minutolo, Filippo
• Is Part Of: ChemMedChem. Volume 13:Number 21(2018)
• Page Start: 2251
• Page End: 2265
• Publication Date: 2018-10-09
• Subjects: anticancer agents -- enzymes -- glycolysis -- patents -- transporters; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201800447
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Many tumors exhibit altered metabolic characteristics relative to normal and healthy tissues. Their metabolic profile highlights a strong prevalence of glycolysis over oxidative phosphorylation, regardless of their exposure to different oxygen levels (the Warburg effect). This condition originates from a set of gene regulations, consisting of the overexpression of some enzymes or transporters involved in the glycolytic pathway. Therefore, these effectors may constitute appealing targets for the implementation of selective therapeutic interventions against cancer. Recently, significant progress has been made in the discovery of molecules that act at various levels of the glycolytic pathway of tumor cells. So far, some of the most widely explored targets of the glycolytic cascade are represented by glucose transporters, hexokinase, 6‐phosphofructokinase, enolase, pyruvate kinase, lactate dehydrogenase, and monocarboxylate transporters. The purpose of this minireview is to provide an update on some of the most recently patented bioactive molecules that are able to interfere with cancer glycolysis, and on their use in specific combination therapies. Abstract : Proliferating cancer cells are characterized by an altered energetic metabolism that exploits glycolysis as the preferential energy source. This glycolytic addiction offers therapeutic opportunities for cancer treatment, as glycolytic enzymes and transporters are overexpressed. Glucose transporter (GLUT), hexokinase (HK), 6‐phosphofructo‐2‐kinase/fructose‐2, 6‐bisphosphatase (PFKFB), phosphofructokinase (PFK), enolase (ENO), pyruvate kinase (PK), lactate dehydrogenase (LDH), and monocarboxylate transporters (MCT) are the main glycolytic effectors targeted by patented small molecules with the aim of interfering with the peculiar metabolism of tumors.