Direct inhibition of c-Myc-Max heterodimers by celastrol and celastrol-inspired triterpenoids

• Published in: Oncotarget Vol. 6; no. 32; pp. 32380 - 32395
• Main Authors: Wang, Huabo, Teriete, Peter, Hu, Angela, Raveendra-Panickar, Dhanya, Pendelton, Kelsey, Lazo, John S, Eiseman, Julie, Holien, Toril, Misund, Kristine, Oliynyk, Ganna, Arsenian-Henriksson, Marie, Cosford, Nicholas D P, Sundan, Anders, Prochownik, Edward V
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 20.10.2015
• Subjects: Antineoplastic Agents, Phytogenic - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - antagonists & inhibitors; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Design; Humans; Medicin och hälsovetenskap; Molecular Targeted Therapy; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Priority Research Paper; Protein Binding; Protein Multimerization; Protein Structure, Quaternary; Proto-Oncogene Proteins c-myc - antagonists & inhibitors; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Signal Transduction - drug effects; Structure-Activity Relationship; Time Factors; Transfection; Triterpenes - metabolism; Triterpenes - pharmacology; Tumor Cells, Cultured; quinone methide; neuroblastoma; 10074-G5; myeloma; 10058-F4; BET inhibitors

Many oncogenic signals originate from abnormal protein-protein interactions that are potential targets for small molecule inhibitors. However, the therapeutic disruption of these interactions has proved elusive. We report here that the naturally-occurring triterpenoid celastrol is an inhibitor of th...