5.31552

Argonaute-2 Inhibitor, BCI-137

• 別名: Argonaute-2 Inhibitor, BCI-137, 2-(2,3-Dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamido) propanoic acid, N-((2,3-Dihydroxy-6-quinoxalinyl)sulfonyl)alanine, Ago2 Inhibitor, BCI137
• 実験式（ヒル表記法）: C₁₁H₁₁N₃O₆S
• CAS番号: 112170-24-8
• 分子量: 313.29
• UNSPSCコード: 12352200
• PubChem Substance ID: 3157172
• NACRES: NA.77

特性

• アッセイ: ≥97% (HPLC)
• 品質水準: 100
• 形状: solid
• 有効性: 126 μM K_d
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: gray-white
• 溶解性: DMSO: 100 mg/mL
• 保管温度: 2-8°C
• SMILES記法: CC(C(=O)O)NS(=O)(=O)C1=CC2=C(C=C1)NC(=O)C(=O)N2

詳細

詳細

A cell-permeable dioxotetrahydroquinoxaline compound that mimics uridine monophosphate for affinity interaction at the Argonaute-2 (Ago2) Mid domain (K_D = 126 µM) and effectively inhibits Ago2 cellular miRNA loading in acute promyelocytic leukemia (APL) NB4 cultures (% inhibition by RIP = 79%/miR-107, 73%/let-7a, 73%/miR-223, 68%/miR-26a, 53%/miR-60a; 100 nM for 48 h) without affecting cellular Ago2 stability. Consistent with the involvement of Ago2 in heterochromatic miR-155HG silencing, BCI-137 is reported to decrease miR-155HG promoter region-associated Ago2 with a concomitant acetylation induction of the promoter region-associated histone H4 (70% reduced Ago2 association and 300% enhanced H4 acetylation, respectively, by ChIP; 10 µM). Likewise, Ago2 inhibition by BCI-137 is shown to boost Retinoic Acid-(RA, Cat. no. 554720) induced NB4 granulocyte differentiation as a result of greatly upregulated expression of the differentiation-related miRNAs (140% and 255% increased miR-26a and miR-223 level, respectively, compared to 100 nM RA stimulation alone for 96 h) without affecting NB4 proliferation or viability (up to 10 µM and 96 h with or without 100 nM RA stimulation).

A cell-permeable, non-toxic dioxotetrahydroquinoxaline compound that mimics uridine and directly and reversibly interacts with the microRNA (miRNA) binding domain of Argonaute-2 (Ago2; K_D = 126 µM) and significantly inhibits binding of miR-20a, miR-26a, miR-107, miR-223, and let-7a to Ago2. However, it does not affect Ago2 stability in cells. Displaces Ago2 from the miR-155 host gene promoter region (70% reduction in Ago2 association) and increases histone H4 acetylation (~300%) in NB4 leukemia cell line. Promotes retinoic acid-induced differentiation of NB4 cells to granulocytes.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
Argonaute-2

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

Masciarelli, S., et al. 2014. ACS Chem. Biol.9, 1674.

法的情報

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

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable