509911 RNA Polymerase I Inhibitor II, BMH-21 - Calbiochem

509911
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      Overview

      Replacement Information

      Key Specifications Table

      Empirical Formula
      C₂₁H₂₀N₄O₂

      Pricing & Availability

      Catalog NumberAvailability Packaging Qty/Pack Price Quantity
      5.09911.0001
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          Glass bottle 10 mg
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          Description
          OverviewA cell-permeable, non-toxic, benzopyridoquinazoline-carboxamide compound that blocks the growth and viability of a variety of cancer cell lines (GI50 = 160 nM in NCI-60 cells), but does not significantly affect normal cells (~90-fold therapeutic window). Preferentially binds to the GC-rich DNA and inhibits RNA polymerase I (Pol I) transcription. Although it intercalates with DNA, it does not activate the DNA damage response. Induces a proteasome-dependent destruction of large Pol I catalytic subunit RPA194, independent of TP53 genetic status of cancer cells, leading to disassembly of Pol I holocomplex from the rDNA. However, it does not affect Rpb1, the large subunit of RNA polymerase II and Pol I preinitiation complex proteins. Effectively reduces the growth of A375 and HCT116 xenografts in athymic NCr nu/nu mice (50 mg/kg, i.p, 2 weeks).

          Please note that the molecular weight for this compound is batch-specific due to variable water content.
          Catalogue Number509911
          Brand Family Calbiochem®
          SynonymsN-(2-(Dimethylamino)ethyl)-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide, BMH21, rRNA Transcription Inhibitor II
          References
          ReferencesPeltonen, K., et al. 2014. Cancer Cell 25, 77.
          Peltonen, K., et al. 2010. PLoS One 5, e12996.
          Product Information
          FormOrange-yellow powder
          Hill FormulaC₂₁H₂₀N₄O₂
          Chemical formulaC₂₁H₂₀N₄O₂
          ReversibleY
          Applications
          Biological Information
          Primary TargetrDNA
          Purity≥98% by HPLC
          Physicochemical Information
          Cell permeableY
          Dimensions
          Materials Information
          Toxicological Information
          Safety Information according to GHS
          Safety Information
          Product Usage Statements
          Storage and Shipping Information
          Ship Code Ambient Temperature Only
          Toxicity Standard Handling
          Storage +2°C to +8°C
          Protect from Light Protect from light
          Do not freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Packaging Information
          Packaged under inert gas Packaged under inert gas
          Transport Information
          Supplemental Information
          Specifications

          Documentation

          SDS

          Title

          Safety Data Sheet (SDS) 

          References

          Reference overview
          Peltonen, K., et al. 2014. Cancer Cell 25, 77.
          Peltonen, K., et al. 2010. PLoS One 5, e12996.
          Data Sheet

          Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

          Revision04-June-2014 JSW
          SynonymsN-(2-(Dimethylamino)ethyl)-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide, BMH21, rRNA Transcription Inhibitor II
          DescriptionA cell-permeable, reversible DNA-intercalating benzopyridoquinazoline-carboxamide that preferentially targets GC-rich sequence, notably that of rDNA (162% of average human genome GC content), and effectively inhibits RNA polymerase I- (Pol I) mediated rDNA transcription both in cell-free assays and in cultures (IC50/ICmax = 60 nM/≤1 µM against 2-h de novo 47S transcription in A375 cells) without affecting the maturation/processing of 47S into 32S and 18S rRNA. Time-dependent studies in 1 µM BMH-21-treated A375 cells reveal fast inhibition of nuclear RNA synthesis (FUrd incorporation) within 15 min, followed by progressive altered localization of nucleolar proteins (starting in <20 min), including Pol I subunit RPA194 capping structure formation, indicative of stalled Pol I complex, and eventual proteasome-mediated RPA194 degradation (>1 h). Although BMH-21 activates p53 independent of DNA damage-sensing ATM pathway signaling in A375 cultures, wt p53 is not a prerequisite for BMH-21 anticancer activity (Av GI50 = 110 nM/wt and 205 nM/mutant among NCI60 cancer panel). Intraperitoneal injection is demonstrated to be efficacious in suppressing A375 (25 & 50 mg/kg/d, 6d/wk) and HCT-116 (50 mg/kg/d, 7 d/wk) tumor growth in mice in vivo. MG-132 (Cat. Nos. 474790, 474787, 474788, and 474791) effectively prevents BMH-21-induced RPA194 degradation without restoring stalled rRNA synthesis.
          FormOrange-yellow powder
          Intert gas (Yes/No) Packaged under inert gas
          Chemical formulaC₂₁H₂₀N₄O₂
          Purity≥98% by HPLC
          SolubilityDMSO (1 mg/ml) or 5% Aqueous Acetic Acid (25 mg/ml)
          Storage +2°C to +8°C
          Protect from light
          Do Not Freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Toxicity Standard Handling
          ReferencesPeltonen, K., et al. 2014. Cancer Cell 25, 77.
          Peltonen, K., et al. 2010. PLoS One 5, e12996.