BMH-21 | RNA Polymerase I inhibitor

BMH-21 (896705-16-1) is a planar heterocyclic DNA intercalator that inhibits RNA polymerase I (Pol I), IC₅₀ = 0.6 µM in U2OS cells, but not Pols II or III, blocking transcription elongation without inducing the DNA damage response.^1-3 Inhibition disengages Pol I from chromatin, resulting in proteasome-dependent destruction of Pol I subunit RPA194.⁴ At nanomolar concentrations it also activates p53 in A375 cells.⁵

References/Citations:

1. Colis et al. (2014), DNA intercalator BMH-21 inhibits RNA polymerase I independent DNA damage response; Oncotarget, 5 4361
2. Jacobs et al. (2022), RNA Polymerase I is Uniquely Vulnerable to the Small-Molecule Inhibitor BMH-21; Cancers (Basel), 14 5544
3. Jacobs et al. (2022), The small-molecule BMH-21 directly inhibits transcription elongation and DNA occupancy of RNA polymerase I in vivo and in vitro; J. Biol.  Chem, 298 101450
4. Wei et al. (2018), Small-molecule targeting of RNA Polymerase I Activates a Conserved Transcription Elongation Checkpoint; Cell Rep. 23 404
5. Peltonen et al. (2010), Identification of novel p53 pathway activating small-molecule compounds reveals unexpected similarities with known therapeutic reagents; PLoS One 5 e12996