Cancer metabolism

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Structures of lactate dehydrogenase A (LDHA) in apo, ternary and inhibitor-bound forms

Lactate dehydrogenase (LDH) is an essential metabolic enzyme that catalyzes the interconversion of pyruvate and lactate using NADH/NAD(+) as a co-substrate. Many cancer cells exhibit a glycolytic phenotype known as the Warburg effect, in which elevated LDH levels enhance the conversion of glucose to lactate, making LDH an attractive therapeutic target for oncology. Two known [...]

January 23rd, 2015|Tags: , , , |

Alectos Announces Preclinical Data for Novel Cancer Metabolism Target

May 22, 2014 – Alectos today announced publication of preclinical studies showing that both knockdown and pharmacological inhibition of O-GlcNAc transferase (OGT) result in reduced metabolic output, increased apoptosis, and impaired survival in tumor cells.  This data strongly supports OGT as a novel cancer metabolism target. For details, see: Ferrer, C.M. et al. Mol Cell [...]

May 22nd, 2014|Tags: , , , |

O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway

The hexosamine biosynthetic pathway elevates posttranslational addition of O-linked β-N-acetylglucosamine (O-GlcNAc) on intracellular proteins. Cancer cells elevate total O-GlcNAcylation by increasing O-GlcNAc transferase (OGT) and/or decreasing O-GlcNAcase (OGA) levels. Reducing O-GlcNAcylation inhibits oncogenesis. Here, we demonstrate that O-GlcNAcylation regulates glycolysis in cancer cells via hypoxia-inducible factor 1 (HIF-1α) and its transcriptional target GLUT1. Reducing O-GlcNAcylation [...]

May 22nd, 2014|Tags: , , |

Alectos Supports NSERC Funding for Prof. B.M. Pinto at SFU

July 16, 2012 – Alectos today announced its support for NSERC funding for the group of Prof. B.M. Pinto at Simon Fraser University, Department of Chemistry, in a project titled “Molecular dynamics simulations of Ligand-Enzyme complexes for a novel target involved in cancer metabolism". The collaboration between Alectos Therapeutics and the Pinto group at SFU [...]

July 16th, 2012|Tags: , , , |

Alectos Supports NSERC Funding for Prof. L. Craig at SFU

April 30, 2012 – Alectos today announced its support for NSERC funding for the group of Prof. L. Craig at Simon Fraser University, Department of Molecular Biology and Biochemistry, in a project titled “Structural analysis of small molecule inhibitors of a novel target for the treatment of cancer". Compared to normal cells, cancer cells exhibit [...]

April 30th, 2012|Tags: , , , |

Alectos Supports NSERC Funding for Prof. R.A. Britton at SFU

Feb 1, 2012 – Alectos today announced its support for NSERC funding for the group of Prof. R.A. Britton at Simon Fraser University, Department of Chemistry, in a project titled “Synthesis of small molecule modulators of cancer metabolism". Cancer is a worldwide health problem and is the leading cause of death in Canada. Novel treatment [...]

February 1st, 2012|Tags: , , , |

Hijacking a biosynthetic pathway yields a glycosyltransferase inhibitor within cells

Glycosyltransferases are ubiquitous enzymes that catalyze the assembly of glycoconjugates throughout all kingdoms of nature. A long-standing problem is the rational design of probes that can be used to manipulate glycosyltransferase activity in cells and tissues. Here we describe the rational design and synthesis of a nucleotide sugar analog (Ac-5SGlcNAc) that inhibits, with high potency [...]

January 23rd, 2011|Tags: , , , |