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Usage

Uses

Used in Pharmaceutical Industry:
BMH21 is used as a research compound for studying the interactions between small molecules and DNA. Its DNA intercalating properties make it a valuable tool in understanding the mechanisms of action for potential therapeutic agents.
Used in Cell Culture Applications:
In cell culture, BMH21 is utilized to investigate the effects of DNA intercalation on cellular processes. This can provide insights into the development of new drugs and therapies that target DNA-related pathways or mechanisms.
Used in Cancer Research:
BMH21 is used as a chemotherapeutic agent in cancer research. Its ability to intercalate with DNA can lead to the inhibition of DNA replication and transcription, which can be leveraged to target rapidly dividing cancer cells and potentially halt tumor growth.
Used in Molecular Biology:
BMH21 is used as a molecular probe in molecular biology to study DNA structure, function, and interactions with other molecules. This can contribute to a broader understanding of genetic information and its manipulation for various applications.

Biochem/physiol Actions

BMH-21 is a potent inhibitor of RNA Pol I. BMH-21 binds strongly to GC-rich DNA sequences, ultimately inhibiting RNA Pol I, blocking transcription and disrupting the nucleolar structure. BMH-1 causes dissociation of the RPA194 catalytic subunit from Pol I, and disassembly of Pol I:DNA complexes. The compound BMH-21 inhibits proliferation of a broad range of tumor cell lines.

Upstream product

• 2942-59-8 2-chloronicotinic acid 
• 5959-52-4 2-Amino-3-naphthoic acid 
• 108-00-9 N,N-dimethylethylenediamine 
• 63127-04-8 12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxylic acid 

Relevant academic research and scientific papers

COMPOUNDS WHICH INHIBIT RNA POLYMERASE, COMPOSITIONS INCLUDING SUCH COMPOUNDS, AND THEIR USE

RNA polymerase I (Pol I) is a dedicated polymerase for the transcription of the 47S ribosomal RNA precursor subsequently processed into the mature 5.8S, 18S and 28S ribosomal RNAs and assembled into ribosomes in the nucleolus. Pol I activity is commonly deregulated in human cancers. Based on the discovery of lead molecule BMH-21, a series of pyridoquinazolinecarboxamides were synthesized as inhibitors of Pol I and activators of the destruction of RPA194, the Pol I large catalytic subunit protein. The present invention identifies a set of bioactive compounds, including purified stereoisomers, that potently cause RPA194 degradation that function in a tightly constrained chemical space. Pharmaceutical compositions comprising these compounds and their uses in cancer and other Pol I related diseases is also provided.

Design, synthesis, and structure-activity relationships of pyridoquinazolinecarboxamides as RNA polymerase i inhibitors

RNA polymerase I (Pol I) is a dedicated polymerase that transcribes the 45S ribosomal (r) RNA precursor. The 45S rRNA precursor is subsequently processed into the mature 5.8S, 18S, and 28S rRNAs and assembled into ribosomes in the nucleolus. Pol I activity is commonly deregulated in human cancers. On the basis of the discovery of lead molecule BMH-21, a series of pyridoquinazolinecarboxamides have been evaluated as inhibitors of Pol I and activators of the destruction of RPA194, the Pol I large catalytic subunit protein. Structure-activity relationships in assays of nucleolar stress and cell viability demonstrate key pharmacophores and their physicochemical properties required for potent activation of Pol I stress and cytotoxicity. This work identifies a set of bioactive compounds that potently cause RPA194 degradation that function in a tightly constrained chemical space. This work has yielded novel derivatives that contribute to the development of Pol I inhibitory cancer therapeutic strategies.