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Overview
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Background
BMH-21 is a planar heterocyclic small molecule DNA intercalator with inhibition of Pol I activity at IC50 = 0.06 µM. [1]DNA interaction is a well-recognized property for several classes of cancer drugs, which interact with the duplex DNA with three typical binding modalities, namely DNA intercalation, groove binding and covalent interactions. [1]BMH-21 intercalated into dsDNA and had binding preference towards GC-rich DNA sequences. BMH-21 had wide cytotoxic activities against human cancer cell lines, and acted in p53-independent manner, widely considered as a mediator of many cytotoxic agents. BMH-21 played as a novel agent that inhibited transcription of RNA polymerase I (Pol I) by binding to ribosomal (r) DNA that caused Pol I blockade and degradation of the large catalytic subunit of Pol I, RPA194. BMH-21 led to the dissolution of the nucleolar structure. [1] BMH-21 clearly induced p53 expression in the epithelial compartment of human prostate tissues indicating tissue permeability. [2]
[1]. Colis L, Peltonen K, Sirajuddin P et al. DNA intercalator BMH-21 inhibits RNA polymerase I independent of DNA damage response. Oncotarget. 2014 Jun 30;5(12):4361-9.
[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. 2010 Sep 27;5(9):e12996.
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