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Hdm2 Antagonist Mi-219 (Spiro-Oxindole), But Not Nutlin-3 (Cis-Imidazoline), Regulates P53 Through Enhanced Hdm2 Autoubiquitination And Degradation In Human Malignant B-Cell Lymphomas, Angela M. Sosin, Angelika M. Burger, Aisha Siddiqi, Judith Abrams, Ramzi M. Mohammad, Ayad M. Al-Katib

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, thereby compromising p53 activity. Therefore, lymphoma is a suitable model for studying the therapeutic value of disrupting the HDM2-p53 interaction by small-molecule inhibitors (SMIs). HDM2 have been developed and are under various stages of preclinical and clinical investigation. Previously, we examined the anti-lymphoma activity of MI-319, the laboratory grade of a new class of HDM2 SMI, the spiro-oxindole, in follicular lymphoma. Since then, MI-219, the clinical grade has become readily available. This study further examines the preclinical effects and mechanisms of MI-219 in a panel of human lymphoma …