7-硝基吲哚-2-甲酸 T6456

Product Introduction
Bioactivity


英文名: CRT0044876

描述: CRT0044876 (7-NO2-ICA) 是一种高选择性的嘌呤/嘧啶核苷核酸内切酶 1 抑制剂，IC50约为 3 μM。它也是 APE1 所属的核酸外切酶 III 家族的特异性抑制剂，可抑制 APE1 的 AP 内切酶、3′-磷酸二酯酶和 3′-磷酸酶活性，可增强几种 DNA 碱基靶向化合物的细胞毒性。

细胞实验: HT1080 fibrosarcoma cells are grown in 2% RPMI medium [supplemented with penicillin 0.06 g/l, streptomycin 0.1 g/l (pH 7.0), 10% fetal bovine serum and 4 mM glutamine]. Only cells with a plating efficiency of ≥60% are used for clonogenic survival analysis. Tissue culture dishes (10 cm) are seeded with 500 cells per dish and the culture is maintained in a humidified incubator at 37°C in an atmosphere of 5% CO2 and 95% air. To evaluate the toxicity profile of putative APE1 inhibitors, various concentrations (100–500 μM) of inhibitor are added to the medium, and cultures were incubated for 7-10 days until cell colonies are formed. Colonies are fixed [75% (v/v) methanol, 25% (v/v) acetic acid] for 30 min and stained with crystal violet (1 mg/ml in distilled water) for 4 h at room temperature. Visible colonies are counted on a colony counter. (Only for Reference)

激酶实验: AP site cleavage assay: BER reaction buffer comprises 40 mM HEPES–KOH (pH 7.8), 5 mM MgCl2, 0.5 mM DTT and 0.1 mM EDTA. A 10 μl AP site cleavage reaction comprised of BER buffer mix, purified protein (3.3 nM final concentration of APE1) and 0.75 ng reduced AP site double-stranded oligonucleotide. The mixture is incubated at 37°C for 1 h. A total of 1 μl of stop buffer (50% glycerol, 10 mM Tris–HCl, 1 mM EDTA, 0.1% bromophenol blue and 0.1% Xylene cyanol) is added, and the sample mixture is denatured at 90–100°C for 2 min. The sample is then run on a 15% TBE Criterion? Pre-Cast Gel, with electrophoresis at a constant current of 30 mA for 30 min, and the radiolabeled substrate and reaction products are visualized using a phosphorImager. The inhibitory activity of potential APE1-targeting compounds are analyzed at drug concentrations ranging from 0.1 to 100 μM. The resolved radiolabeled bands are quantified using ImageQuant software analysis, and IC50 values are calculated by determining the concentration of the inhibitor that reduced APE1 activity to 50% of the control values.

体外活性: CRT0044876 potently inhibits the AP endonuclease, 3'-phosphodiesterase and 3'-phosphatase activities of APE1, and exhibits the selectivity for the inhibition of exonuclease III family. CRT0044876 potentiates the cytotoxicity of several DNA base-targeting compounds with an accumulation of unrepaired AP sites. [1] CRT0044876, by inhibition of the BER pathway increases oxidative DNA damage temporally related to increased intracellular reactive oxygen species in an acidic tumor microenvironment, and thus results in cell cycle arrests and increased DNA double strand breaks, leading to cell death. [2]

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 39 mg/mL (189.2 mM)
Ethanol : 1 mg/mL (4.85 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)


关键字: CRT-0044876 | non-toxic | CRT 0044876 | DNA | Inhibitor | base | exonuclease | CRT0044876 | inhibit | endonuclease | DNA/RNA Synthesis | NSC-69877 | excision | NSC69877 | repair

相关产品: Fidaxomicin | Tegafur | BCH001 | Adenine | 5-methoxyflavone | 1-Decarboxy-3-oxo-ceanothic acid | hDHODH-IN-12 | 5-Fluorouracil | Flucytosine | Ganoderic acid C1

相关库: Anti-Aging Compound Library | Cell Cycle Compound Library | Anti-Cancer Compound Library | Bioactive Compounds Library Max | Inhibitor Library | Highly Selective Inhibitor Library | DNA Damage & Repair Compound Library | Target-Focused Phenotypic Screening Library | NO PAINS Compound Library | Bioactive Compound Library

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