BMH-21

BMH-21 is a potent small molecule DNA intercalator. BMH-21 binds ribosomal DNA and inhibits RNA polymerase I (Pol I) transcription. BMH-21 does not cause phosphorylation of H2AX, a key biomarker activated in DNA damage stress. BMH-21 effects on the nucleolar stress response were independent of major DNA damage associated PI3-kinase pathways, ATM, ATR and DNA-PKcs. BMH-21 is a chemically unique DNA intercalator that has high bioactivity towards Pol I inhibition without activation or dependence of DNA damage stress. The findings also show that interference with DNA and DNA metabolic processes can be exploited therapeutically without causing DNA damage.

Product information

CAS Number: 896705-16-1

Molecular Weight: 362.42

Formula: C21H22N4O2

Synonym:

BMH21

BMH 21

BMH-21

Chemical Name: N-(2-(dimethylamino)ethyl)-12-oxo-11a,12-dihydro-5aH-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide

Smiles: CN(C)CCNC(=O)C1=CC=CN2C1=NC1C=C3C=CC=CC3=CC1C2=O

InChiKey: FSCFXXLAGKOPMP-UHFFFAOYSA-N

InChi: InChI=1S/C21H22N4O2/c1-24(2)11-9-22-20(26)16-8-5-10-25-19(16)23-18-13-15-7-4-3-6-14(15)12-17(18)21(25)27/h3-8,10,12-13,17-18H,9,11H2,1-2H3,(H,22,26)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

BMH-21 binds ribosomal DNA and inhibits RNA polymerase I (Pol I) transcription. BMH-21 inhibits RNA polymerase I independent of DNA damage response. BMH-21 inhibits 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 intercalates into double strand (ds) DNA and has binding preference towards GC-rich DNA sequences. BMH-21 (1 μM; 3 h ours) acts in a DNA damage independent manner to activate nucleolar stress and RPA194 degradation.

In Vivo:

BMH-21 (50 mg/kg; i.p.; daily, for 6 days) inhibits HCT116 colon cancer tumor growth in vivo.

References:

1. Colis L, Peltonen K, Sirajuddin P, Liu H, Sanders S, Ernst G, Barrow JC, Laiho M. DNA intercalator BMH-21 inhibits RNA polymerase I independent of DNA damage response. Oncotarget. 2014 Jun 30;5(12):4361-9. PubMed PMID: 24952786; PubMed Central PMCID: PMC4147329.
2. Peltonen K, Colis L, Liu H, Trivedi R, Moubarek MS, Moore HM, Bai B, Rudek MA, Bieberich CJ, Laiho M. A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. Cancer Cell. 2014 Jan 13;25(1):77-90. doi: 10.1016/j.ccr.2013.12.009. PubMed PMID: 24434211; PubMed Central PMCID: PMC3930145.

Products are for research use only. Not for human use.