3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one and Neoplasms

3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one has been researched along with Neoplasms* in 4 studies

Reviews

1 review(s) available for 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one and Neoplasms

ArticleYear
An update on therapeutic opportunities offered by cancer glycolytic metabolism.
    Bioorganic & medicinal chemistry letters, 2014, Nov-01, Volume: 24, Issue:21

    Almost all invasive cancers, regardless of tissue origin, are characterized by specific modifications of their cellular energy metabolism. In fact, a strong predominance of aerobic glycolysis over oxidative phosphorylation (Warburg effect) is usually associated with aggressive tumour phenotypes. This metabolic shift offers a survival advantage to cancer cells, since they may continue to produce energy and anabolites even when they are exposed to either transient or permanent hypoxic conditions. Moreover, it ensures a high production rate of glycolysis intermediates, useful as building blocks for fast cell proliferation of cancer cells. This peculiar metabolic profile may constitute an ideal target for therapeutic interventions that selectively hit cancer cells with minimal residual systemic toxicity. In this review we provide an update about some of the most recent advances in the discovery of new bioactive molecules that are able to interfere with cancer glycolysis.

    Topics: Animals; Antineoplastic Agents; Glycolysis; Humans; Neoplasms

2014

Other Studies

3 other study(ies) available for 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one and Neoplasms

ArticleYear
Tumor vessel disintegration by maximum tolerable PFKFB3 blockade.
    Angiogenesis, 2017, Volume: 20, Issue:4

    Blockade of the glycolytic activator PFKFB3 in cancer cells (using a maximum tolerable dose of 70 mg/kg of the PFKFB3 blocker 3PO) inhibits tumor growth in preclinical models and is currently being tested as a novel anticancer treatment in phase I clinical trials. However, a detailed preclinical analysis of the effects of such maximum tolerable dose of a PFKFB3 blocker on the tumor vasculature is lacking, even though tumor endothelial cells are hyper-glycolytic. We report here that a high dose of 3PO (70 mg/kg), which inhibits cancer cell proliferation and reduces primary tumor growth, causes tumor vessel disintegration, suppresses endothelial cell growth for protracted periods, (model-dependently) aggravates tumor hypoxia, and compromises vascular barrier integrity, thereby rendering tumor vessels more leaky and facilitating cancer cell intravasation and dissemination. These findings contrast to the effects of a low dose of 3PO (25 mg/kg), which induces tumor vessel normalization, characterized by vascular barrier tightening and maturation, but reduces cancer cell intravasation and metastasis. Our findings highlight the importance of adequately dosing a glycolytic inhibitor for anticancer treatment.

    Topics: Animals; Cell Line, Tumor; Cell Proliferation; Endothelial Cells; Human Umbilical Vein Endothelial Cells; Humans; Melanoma, Experimental; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Pancreatic Neoplasms; Phosphofructokinase-2; Pyridines

2017
Block copolymer micelles for controlled delivery of glycolytic enzyme inhibitors.
    Pharmaceutical research, 2012, Volume: 29, Issue:3

    To develop block copolymer micelles as an aqueous dosage form for a potent glycolytic enzyme inhibitor, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO).. The micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) [PEG-p(HYD)] block copolymers to which 3PO was conjugated through an acid-labile hydrazone bond. The optimal micelle formulation was determined following the screening of block copolymer library modified with various aromatic and aliphatic pendant groups. Both physical drug entrapment and chemical drug conjugation methods were tested to maximize 3PO loading in the micelles during the screening.. Particulate characterization showed that the PEG-p(HYD) block copolymers conjugated with 3PO (2.08∼2.21 wt.%) appeared the optimal polymer micelles. Block copolymer compositions greatly affected the micelle size, which was 38 nm and 259 nm when 5 kDa and 12 kDa PEG chains were used, respectively. 3PO release from the micelles was accelerated at pH 5.0, potentiating effective drug release in acidic tumor environments. The micelles retained biological activity of 3PO, inhibiting various cancer cells (Jurkat, He-La and LLC) in concentration ranges similar to free 3PO.. A novel micelle formulation for controlled delivery of 3PO was successfully prepared.

    Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Delayed-Action Preparations; Enzyme Inhibitors; Glycolysis; Humans; Mice; Micelles; Nanoconjugates; Neoplasms; Phosphofructokinase-2; Polyethylene Glycols; Proteins; Pyridines

2012
Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth.
    Molecular cancer therapeutics, 2008, Volume: 7, Issue:1

    6-phosphofructo-1-kinase, a rate-limiting enzyme of glycolysis, is activated in neoplastic cells by fructose-2,6-bisphosphate (Fru-2,6-BP), a product of four 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isozymes (PFKFB1-4). The inducible PFKFB3 isozyme is constitutively expressed by neoplastic cells and required for the high glycolytic rate and anchorage-independent growth of ras-transformed cells. We report herein the computational identification of a small-molecule inhibitor of PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), which suppresses glycolytic flux and is cytostatic to neoplastic cells. 3PO inhibits recombinant PFKFB3 activity, suppresses glucose uptake, and decreases the intracellular concentration of Fru-2,6-BP, lactate, ATP, NAD+, and NADH. 3PO markedly attenuates the proliferation of several human malignant hematopoietic and adenocarcinoma cell lines (IC50, 1.4-24 micromol/L) and is selectively cytostatic to ras-transformed human bronchial epithelial cells relative to normal human bronchial epithelial cells. The PFKFB3 enzyme is an essential molecular target of 3PO because transformed cells are rendered resistant to 3PO by ectopic expression of PFKFB3 and sensitive to 3PO by heterozygotic genomic deletion of PFKFB3. Importantly, i.p. administration of 3PO (0.07 mg/g) to tumor-bearing mice markedly reduces the intracellular concentration of Fru-2,6-BP, glucose uptake, and growth of established tumors in vivo. Taken together, these data support the clinical development of 3PO and other PFKFB3 inhibitors as chemotherapeutic agents.

    Topics: Animals; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Female; Glycolysis; Humans; Mice; Mice, Inbred C57BL; Models, Molecular; Molecular Structure; Neoplasms; Phosphofructokinase-2; Protein Kinase Inhibitors; Pyridines; Recombinant Proteins; Xenograft Model Antitumor Assays

2008