Serdemetan antagonizes the Mdm2-HIF1α axis leading to decreased levels of glycolytic enzymes

• Published in: PloS one Vol. 8; no. 9; p. e74741
• Main Authors: Lehman, Jason A, Hauck, Paula M, Gendron, Jaimie M, Batuello, Christopher N, Eitel, Jacob A, Albig, Allan, Kadakia, Madhavi P, Mayo, Lindsey D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.09.2013; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Apoptosis; Biochemistry; Brain cancer; Brain Neoplasms - enzymology; Cell Line, Tumor - drug effects; Cell Survival; Enzymes; Fluorides; Gene expression; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - enzymology; Glioblastoma cells; Glucose transporter; Glycolysis; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors; MDM2 protein; Medicine; Molecular biology; p53 Protein; Pediatrics; Phosphopyruvate hydratase; Proteins; Proto-Oncogene Proteins c-mdm2 - antagonists & inhibitors; Rodents; Side effects; Tryptamines - pharmacology; Tumor Suppressor Protein p53 - metabolism; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Indiana; United States > US; Indianapolis Indiana

Serdemetan (JNJ-26854165), an antagonist to Mdm2, was anticipated to promote the activation of p53. While regulation of p53 by Mdm2 is important, Mdm2 also regulates numerous proteins involved in diverse cellular functions. We investigated if Serdemetan would alter the Mdm2-HIF1α axis and affect cel...