CRT0044876

APE1 inhibitor, potent and selective CAS# 6960-45-8

CRT0044876

Catalog No. BCC5109----Order now to get a substantial discount!

Product Name & Size Price Stock
CRT0044876: 5mg $23 In Stock
CRT0044876: 10mg Please Inquire In Stock
CRT0044876: 20mg Please Inquire Please Inquire
CRT0044876: 50mg Please Inquire Please Inquire
CRT0044876: 100mg Please Inquire Please Inquire
CRT0044876: 200mg Please Inquire Please Inquire
CRT0044876: 500mg Please Inquire Please Inquire
CRT0044876: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of CRT0044876

Number of papers citing our products

Chemical structure

CRT0044876

3D structure

Chemical Properties of CRT0044876

Cas No. 6960-45-8 SDF Download SDF
PubChem ID 6931472 Appearance Powder
Formula C9H6N2O4 M.Wt 206.15
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble in DMSO > 10 mM
Chemical Name 7-nitro-1H-indole-2-carboxylate
SMILES C1=CC2=C(C(=C1)[N+](=O)[O-])NC(=C2)C(=O)[O-]
Standard InChIKey BIUCOFQROHIAEO-UHFFFAOYSA-M
Standard InChI InChI=1S/C9H6N2O4/c12-9(13)6-4-5-2-1-3-7(11(14)15)8(5)10-6/h1-4,10H,(H,12,13)/p-1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

CRT0044876 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

CRT0044876 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of CRT0044876

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 4.8508 mL 24.2542 mL 48.5084 mL 97.0167 mL 121.2709 mL
5 mM 0.9702 mL 4.8508 mL 9.7017 mL 19.4033 mL 24.2542 mL
10 mM 0.4851 mL 2.4254 mL 4.8508 mL 9.7017 mL 12.1271 mL
50 mM 0.097 mL 0.4851 mL 0.9702 mL 1.9403 mL 2.4254 mL
100 mM 0.0485 mL 0.2425 mL 0.4851 mL 0.9702 mL 1.2127 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on CRT0044876

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.

Featured Products
New Products
 

References on CRT0044876

Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair.[Pubmed:24466051]

PLoS One. 2014 Jan 23;9(1):e86358.

Ku70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS) to repair DNA double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. As expected mutating these genes in mice caused a similar DSB repair-defective phenotype. However, ku70(-/-) cells and ku80(-/-) cells also appeared to have a defect in base excision repair (BER). BER corrects base lesions, apurinic/apyrimidinic (AP) sites and single stand breaks (SSBs) utilizing a variety of proteins including glycosylases, AP endonuclease 1 (APE1) and DNA Polymerase beta (Pol beta). In addition, deleting Ku70 was not equivalent to deleting Ku80 in cells and mice. Therefore, we hypothesized that free Ku70 (not bound to Ku80) and/or free Ku80 (not bound to Ku70) possessed activity that influenced BER. To further test this hypothesis we performed two general sets of experiments. The first set showed that deleting either Ku70 or Ku80 caused an NHEJ-independent defect. We found ku80(-/-) mice had a shorter life span than dna-pkcs(-/-) mice demonstrating a phenotype that was greater than deleting the holoenzyme. We also found Ku70-deletion induced a p53 response that reduced the level of small mutations in the brain suggesting defective BER. We further confirmed that Ku80-deletion impaired BER via a mechanism that was not epistatic to Pol beta. The second set of experiments showed that free Ku70 and free Ku80 could influence BER. We observed that deletion of either Ku70 or Ku80, but not both, increased sensitivity of cells to CRT0044876 (CRT), an agent that interferes with APE1. In addition, free Ku70 and free Ku80 bound to AP sites and in the case of Ku70 inhibited APE1 activity. These observations support a novel role for free Ku70 and free Ku80 in altering BER.

HSP90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excision and ATM-mediated DNA repair.[Pubmed:18645008]

Mol Cancer Ther. 2008 Jul;7(7):1985-92.

Inhibition of heat shock protein 90 (HSP90) leads to inappropriate processing of proteins involved in cell survival pathways. We found that HSP90 inhibitor, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG), is synergistic with radiation for non-small cell lung cancer cell lines, NCI-H460 and A549. To establish the optimal schedule for this combination, cells were radiated before, after, or simultaneously with DMAG, and survival was scored by clonogenic assay. The sequence of DMAG administration was critical for synergy with radiation, and pretreatment for 16 h led to maximal synergy. Similar radiosensitization was observed in isogenic cells in which expression of wild-type p53 was silenced by RNA interference, although p53 loss rendered cells overall less radiosensitive. The mechanistic basis for synergy was studied by Western blotting, cell cycle analysis, alkaline comet assay, and direct measurement of the activities of key base excision repair enzymes. Regardless of schedule of administration, DMAG led to degradation of proteins involved in activation of cell survival pathways after radiation, which did not explain the differences in the schedule of administration observed in clonogenic assays. In addition to previously reported decrease in activation of ATM, pretreatment with DMAG blocked activation of base excision repair machinery and activity of key enzymes, apurinic/apyrimidinic endonuclease, and DNA polymerase-beta. Similarly, pretreatment with specific apurinic/apyrimidinic endonuclease inhibitor, CRT0044876, reproduced the effects of DMAG. Thus, administration of HSP90 inhibitors before radiation is critical for optimizing their use as radiosensitizers.

Isolation of a small molecule inhibitor of DNA base excision repair.[Pubmed:16113242]

Nucleic Acids Res. 2005 Aug 19;33(15):4711-24.

The base excision repair (BER) pathway is essential for the removal of DNA bases damaged by alkylation or oxidation. A key step in BER is the processing of an apurinic/apyrimidinic (AP) site intermediate by an AP endonuclease. The major AP endonuclease in human cells (APE1, also termed HAP1 and Ref-1) accounts for >95% of the total AP endonuclease activity, and is essential for the protection of cells against the toxic effects of several classes of DNA damaging agents. Moreover, APE1 overexpression has been linked to radio- and chemo-resistance in human tumors. Using a newly developed high-throughput screen, several chemical inhibitors of APE1 have been isolated. Amongst these, CRT0044876 was identified as a potent and selective APE1 inhibitor. CRT0044876 inhibits the AP endonuclease, 3'-phosphodiesterase and 3'-phosphatase activities of APE1 at low micromolar concentrations, and is a specific inhibitor of the exonuclease III family of enzymes to which APE1 belongs. At non-cytotoxic concentrations, CRT0044876 potentiates the cytotoxicity of several DNA base-targeting compounds. This enhancement of cytotoxicity is associated with an accumulation of unrepaired AP sites. In silico modeling studies suggest that CRT0044876 binds to the active site of APE1. These studies provide both a novel reagent for probing APE1 function in human cells, and a rational basis for the development of APE1-targeting drugs for antitumor therapy.

Description

CRT0044876 is a potent and selective APE1 inhibitor with IC50 of ~3 μM.

Keywords:

CRT0044876,6960-45-8,Natural Products,DNA Synthesis, buy CRT0044876 , CRT0044876 supplier , purchase CRT0044876 , CRT0044876 cost , CRT0044876 manufacturer , order CRT0044876 , high purity CRT0044876

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: