BMH-21

BMH-21 is a synthetic small-molecule DNA intercalator and selective RNA polymerase I (Pol I) transcription inhibitor being developed as an anticancer research compound. It intercalates into GC-rich regions of ribosomal DNA, triggering potent inhibition of Pol I transcription, reduction of Pol I occupancy on rDNA, and destabilization with proteasome-dependent degradation of the large Pol I catalytic subunit (RPA194/A190), thereby inducing a nucleolar stress response and p53 pathway activation without causing a canonical DNA damage response or γH2AX activation.[1][2][5][6][9] In vitro and in vivo mechanistic studies show that BMH-21 most strongly impairs Pol I transcription elongation, increasing pausing upstream of G-rich rDNA sequences and decreasing full-length rRNA synthesis, leading to reduced cancer cell viability and attenuation of tumor growth in xenograft models.[2][5] BMH-21 and its analogs are in preclinical development as first-in-class Pol I transcription-targeting anticancer agents, with reported origin in academic discovery efforts and R&D attribution including Nanchang University.[1][2][7][9]

Other names

BMH 21BMH21BMH-21