Journal article
Second generation RNA Polymerase I inhibitor PMR-116 targets ribsomal RNA synthesis to potently treat a broad spectrum of malignancies
Rita Ferreira, Katherine M Hannan, Konstantin Panov, Thejanni Udumanne, Amee J George, Zaka Yuen, Perlita Poh, Eric Kusnadi, Alisee Huglo, Mitchell Lawrence, Mustapha Haddach, Denis Drygin, Luc Furic, Ross D Hannan, Nadine Hein
MOLECULAR CANCER THERAPEUTICS | AMER ASSOC CANCER RESEARCH | Published : 2024
Abstract
Abstract Purpose and rational for the study: The purpose of the study was to develop novel 2nd generation ribosomal RNA synthesis inhibitors for cancer treatment. Ribosome biogenesis (RiBi) is essential for cell growth and proliferation. Transcription of ribosomal RNA genes by Pol I is a critical step in RiBi and is tightly regulated by tumor suppressors and oncoproteins. Indeed, the ability of the potent oncoprotein, MYC, to drive RiBi is necessary for its oncogenic activity (Bywater et al., Cancer Cell, 2011). These data suggested that targeting RiBi, might be a promising strategy to treat malignancies, especially those driven by MYC. To test this, we developed the 1st small..
View full abstract