CRT0044876 (Synonyms: CRT0044876, 7-Nitroindole-2-Carboxylic Acid, NSC 69877) |
| Catalog No.GC17231 |
APE1 inhibitor, potent and selective
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 6960-45-8
Sample solution is provided at 25 µL, 10mM.
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CRT0044876 is a potent and selective inhibitor of APE1 with IC50 value of 3.06 μM [1].
Apurinic/apyrimidinic endonuclease-1 (APE1) is a member of the highly conserved exonuclease
III family of AP endonucleases and plays an important role in DNA repair. APE1 exhibits 3’-phosphodiesterase activity and weak 3’-phosphatase activity, 3’-5’-exonuclease activity and RNaseH activity [1].
CRT0044876 is a potent and selective APE1 inhibitor. In HeLa whole cell extract, CRT0044876 inhibited apurinic/apyrimidinic (AP) site cleavage catalyzed by APE1. CRT0044876 inhibited both the AP endonuclease and exonuclease activities of exonuclease III, the bacterial homologue of APE1. CRT0044876 inhibited the 3’-phosphoglycolate diesterase activity of APE1 with IC50 value of 5 μM and also inhibited 3’-phosphatase activity through binding to DNA repair active site of APE1. In HT1080 fibrosarcoma cells, CRT0044876 significantly increased AP site accumulation and was non-toxic at concentrations up to 400 μM. Also, CRT0044876 potentiated the cytotoxicity induced by alkylating agent MMS, temozolomide, hydrogen peroxide and hmdUrd through specific inhibition of the base excision repair (BER) pathway [1].
Reference:
[1]. Madhusudan S, Smart F, Shrimpton P, et al. Isolation of a small molecule inhibitor of DNA base excision repair. Nucleic Acids Res, 2005, 33(15): 4711-4724.
| Kinase experiment [1]: | |
|
AP site cleavage assay |
BER reaction buffer comprised 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 was incubated at 37 °C for 1 hr. 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) was added, and the sample mixture was denatured at 90 ~ 100 °C for 2 mins. The sample was then loaded on a 15% TBE Criterion Pre-Cast Gel, with electrophoresis at a constant current of 30 mA for 30 mins, and the radiolabeled substrate and reaction products were visualized using a phosphorImager. The inhibitory activity of potential APE1-targeting compounds was analyzed at drug concentrations ranging from 0.1 to 100 μM. The resolved radiolabeled bands were quantified using ImageQuant software analysis, and IC50 values were calculated. |
| Cell experiment [1]: | |
|
Cell lines |
Human HT1080 fibrosarcoma cells |
|
Preparation method |
The solubility of this compound in DMSO is > 55.6 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
1 ~ 2 hrs |
|
Applications |
In Human HT1080 fibrosarcoma cells, CRT0044876 significantly increased apurinic/apyrimidinic (AP) site accumulation. HT1080 cells treated with methylmethane sulfonate (MMS) also elevated the level of AP sites. The combination of CRT0044876 and MMS caused a synergistic increase in the level of AP sites. |
|
References: [1]. Madhusudan S, Smart F, Shrimpton P, et al. Isolation of a small molecule inhibitor of DNA base excision repair. Nucleic Acids Res, 2005, 33(15): 4711-4724. |
|
| Cas No. | 6960-45-8 | SDF | |
| Synonyms | CRT0044876, 7-Nitroindole-2-Carboxylic Acid, NSC 69877 | ||
| Chemical Name | 7-nitro-1H-indole-2-carboxylic acid | ||
| Canonical SMILES | C1=CC2=C(C(=C1)[N+](=O)[O-])NC(=C2)C(=O)O | ||
| Formula | C9H6N2O4 | M.Wt | 206.15 |
| Solubility | ≥ 55.6mg/mL in DMSO | Storage | Store at -20° C, protect from light |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 4.8508 mL | 24.2542 mL | 48.5084 mL |
| 5 mM | 0.9702 mL | 4.8508 mL | 9.7017 mL |
| 10 mM | 0.4851 mL | 2.4254 mL | 4.8508 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
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