BMH-21

BMH-21 is an inhibitor of RNA polymerase I.¹ It binds to GC-rich sequences in DNA and ribosomal DNA (rDNA) and inhibits RNA polymerase I transcription in vitro. It inhibits expression of the 47S rRNA transcript (IC₅₀ = 60 nM), disrupts the structure of the nucleolus, and leads to removal of the RNA polymerase complex from rDNA by inducing dissociation and destruction of RPA194 through a proteasome-dependent mechanism. BMH-21 also activates p53 in the nanomolar range.² It reduces viability of several cancer cell lines but not of non-cancerous cells (IC₅₀s = 0.7, 1.9, ≥40, and 2.7 µM for A375, human diploid fibroblasts, primary human melanocytes, and HIMEC cells, respectively). BMH-21 intercalates with DNA but does not induce DNA damage via the ataxia-telangiectasia mutated (ATM) kinase pathway. BMH-21 (25 mg/kg) inhibits tumor growth in melanoma and colon cancer mouse xenograft models.¹

WARNING This product is not for human or veterinary use.

1. Peltonen, K., Colis, L., Liu, H., et al. A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. Cancer Cell 25(1), 77-90 (2014).

2. Peltonen, K., Colis, L., Liu, H., et al. Identification of novel p53 pathway activating small-molecule compounds reveals unexpected similarities with known therapeutic agents. PLoS One 5(9), e12996 (2010).