BMH-21

BMH-21 is an inhibitor of RNA polymerase I. It binds to GC-rich sequences in DNA and ribosomal DNA (rDNA) and inhibits RNA polymerase I transcription in vitro. It inhibits expression of the 47S rRNA transcript (IC50 = 60 nM), disrupts the structure of the nucleolus, and leads to removal of the RNA polymerase complex from rDNA by inducing dissociation and destruction of RPA194 through a proteasome-dependent mechanism. BMH-21 also activates p53 in the nanomolar range. It reduces viability of several cancer cell lines but not of non-cancerous cells (IC50s = 0.7, 1.9, >40, and 2.7 µM for A375, human diploid fibroblasts, primary human melanocytes, and HIMEC cells, respectively). BMH-21 intercalates with DNA but does not induce DNA damage via the ataxia-telangiectasia mutated (ATM) kinase pathway. BMH-21 (25 mg/kg) inhibits tumor growth in melanoma and colon cancer mouse xenograft models.Formal Name: N-[2-(dimethylamino)ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide. CAS Number: 896705-16-1. Molecular Formula: C21H20N4O2. Formula Weight: 360.4. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 2 mg/ml, DMF:PBS (pH 7.2)(1:3): 0.25 mg/ml, DMSO: 1 mg/ml, Ethanol: 0.2 mg/ml. lambdamax: 233, 271, 364, 383 nm. SMILES: O=C1N2C(C(C(NCCN(C)C)=O)=CC=C2)=NC(C1=C3)=CC4=C3C=CC=C4. InChi Code: InChI=1S/C21H20N4O2/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/h3-8,10,12-13H,9,11H2,1-2H3,(H,22,26). InChi Key: BXYDVWIAGDJBEC-UHFFFAOYSA-N.