As a leading chemical supplier, BOC Sciences provides various cytotoxin used as payloads to conjugate with antibodies to form ADCs. We are committed to providing competitive prices and timely delivery of our products with guaranteed quality and recognized quality. Furthermore, we offer our customers with comprehensive one-stop-shop of all aspects in ADC development and evaluation. Glycolysis pathway of cellular respiration is a series of reactions that constitute the first phase of most carbohydrate catabolism. It is an oxygen independent metabolic pathway, meaning it does not use molecular oxygen for any of its reactions. Glycolysis produces a large amount of lactic acid. Lactic acid can promote tumor cell proliferation, tumor metastasis, tumor tissue angiogenesis, tumor immune escape and affect the tumor’s chemoradiation effect. Therefore, tumor glycolysis plays a vital role in the occurrence and development of tumors. With changes in the tumor microenvironment, the metabolism of tumor cells is also quite different from that of normal cells. The most significant difference is the Warburg effect, in which, compared with normal cells, tumor cells obtain energy through anaerobic glycolysis even under oxygen-rich conditions (Fig. 1).
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The glycolytic pathway can be divided into two phases. Firstly, the preparatory phase (or investment phase) is where ATP is utilised and followed by production of ATP in the second Pay Off phase. In the cell, glucose catabolism occurs via two main pathways, (1) one which involves mitochondrial respiration (longer but energy-efficient pathway) and (2) pathway that does not involve the mitochondria (glycolysis; less energy-efficient and a shorter pathway). Glycolytic metabolism of glucose results in lactic acid, which can acidify the tumor microenvironment after being expelled by cancer cells. At the same time, hypoxia will lead to increased expression levels of hypoxiainducible factor in cells. This causes high expression of proteases associated with glycolysis. Tumor cells meet the needs of rapid growth and development by glycolysis to produce large amounts of lactic acid and ATP. The acidic environment outside the tumor cells can stimulate cell proliferation, activate transcription factors, enhance the expression of target genes and promote tumorigenesis.
Fig. 1. Aerobic respiration scheme.
Tumor cells mainly provide necessary energy and substances for rapid cell growth through aerobic perglycolysis rather than oxidative phosphorylation. The mechanism of glycolysis in tumor cells is more complicated, which is caused by the comprehensive regulation of multiple factors. Abnormal enzyme metabolism is one of the main influencing factors and inhibiting the three main rate-limiting enzymes in glycolysis is thought to be important strategy for cancer treatment. Therefore, numerous inhibitors of glycolysis rate-limiting enzyme have been developed in recent years, such as the latest HKII inhibitor and PKM2 inhibitor Pachymic acid (PA) and N-(4-(3-(3-(methylamino)-3-oxopropyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-1-yl)phenyl)propiolamide. Glucopiericidin A is a natural piericidin compound obtained from a marine-derived Streptomyces strain, which is widely used as a glycolysis inhibitor for antibody-drug conjugate (ADC) development.