5.09911

RNA Polymerase I Inhibitor II, BMH-21

• 別名: RNA Polymerase I Inhibitor II, BMH-21, BMH21, rRNA Transcription Inhibitor II, N-(2-(Dimethylamino)ethyl)-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide, N-(2-(Dimethylamino)ethyl)-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide, BMH21, rRNA Transcription Inhibitor II
• 実験式（ヒル表記法）: C₂₁H₂₀N₄O₂
• CAS番号: 896705-16-1
• 分子量: 360.41
• MDL番号: MFCD27225377
• UNSPSCコード: 12352200
• NACRES: NA.77

特性

• アッセイ: ≥98% (HPLC)
• 品質水準: 100
• フォーム: powder
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: orange-yellow
• 溶解性: DMSO: 1 mg/mL; 5% acetic acid: 25 mg/mL
• 保管温度: 2-8°C
• SMILES記法: [n]21c(nc3c([c]2=O)cc4c(c3)cccc4)c(ccc1)C(=O)NCCN(C)C
• InChI Key: BXYDVWIAGDJBEC-UHFFFAOYSA-N

詳細

詳細

A 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/IC_max = 60 nM/≤1 M 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 M 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.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
rDNA

Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

その他情報

Peltonen, K., et al. 2014. Cancer Cell25, 77.

Peltonen, K., et al. 2010. PLoS One5, e12996.

法的情報

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

安全性情報

• ピクトグラム: GHS07
• シグナルワード: Warning
• 危険有害性情報: H302
• 注意書き: P264 - P270 - P301 + P312 - P501
• 危険有害性の分類: Acute Tox. 4 Oral
• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable