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: , , |

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: , , , |