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BioAssay: AID 504595

Inhibitors of APE1: Aqueous Solubility Profiling

The apurinic/apyrimidinic endonuclease APE1 is the primary mammalian enzyme responsible for the removal of abasic (or AP) sites in DNA and functions centrally in the base excision DNA repair (BER) pathway. Recent studies suggested a link between an overexpression of APE1 in many cancers and resistance of these tumor cells to radio- and chemotherapy. Thus, targeting APE1 could improve the efficacy of current treatment paradigms by promoting selective sensitization or protection of diseased and normal cells, respectively. ..more
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
AID: 504595
Data Source: NCGC (APE1801)
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2011-03-28
Hold-until Date: 2011-05-01
Modify Date: 2011-05-03

Data Table ( Complete ):           Active    All
Target
BioActive Compound: 1
Depositor Specified Assays
AIDNameTypeComment
1707Counterscreen for APE1 Inhibitors: Fluorescent Dye Displacement Validation AssayconfirmatoryPrimary qHTS assay for APE1 inhibitors
1708Counterscreen for APE1 Inhibitors: qHTS Validation Assay for Inhibitors of Endonuclease IVconfirmatoryEndoIV counterscreen
1705qHTS Validation Assay for Inhibitors of the Human Apurinic/apyrimidinic Endonuclease 1 (APE1)confirmatoryDNA binding counterscreen
2573qHTS FP-Based Assay for Inhibitors of the Human Apurinic/apyrimidinic Endonuclease 1 (APE1)confirmatoryFP counterscreen
2324Probe Development Summary of Inhibitors of the Human Apurinic/apyrimidinic Endonuclease 1 (APE1)summary
Description:
The apurinic/apyrimidinic endonuclease APE1 is the primary mammalian enzyme responsible for the removal of abasic (or AP) sites in DNA and functions centrally in the base excision DNA repair (BER) pathway. Recent studies suggested a link between an overexpression of APE1 in many cancers and resistance of these tumor cells to radio- and chemotherapy. Thus, targeting APE1 could improve the efficacy of current treatment paradigms by promoting selective sensitization or protection of diseased and normal cells, respectively.

This bioassay provides profiling data on aqueous kinetic solubility (PBS @ pH 7.4) of one of the lead compounds developed in the APE1 inhibitors project.

APE1 Project Principal Investigator: David M. Wilson, III, National Institute on Aging, NIH
Screening Center PI: Austin, C.P.
Screening Center: NIH Chemical Genomics Center [NCGC]
Protocol
1. 8ul of reference and test compound stock solution were added to 392ul 100mM phosphate buffer (pH 7.4)

2. Sample tubes were shaken for 1 hr (1000 rpm) at room temperature

3. Samples were centrifuged (10 min at 12000 rpm) to precipitate un-dissolved particles

4. Supernatants were transferred to new tubes

5. Concentration of the supernatant was determined by LC-UV or LC-MS/MS
Comment
Compounds are "active" if solubility is greater than 20; "inconclusive" if solubility is between 10 and 20; "inactive" if solubility is less than 10.

PUBCHEM_ACTIVITY_SCORE is the solubility rounded to the closet whole number.
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1SolubilityKinetic aqueous solubility (PBS at pH 7.4)FloatμM
2Compound QCSource of compound QCString
Additional Information
Grant Number: MH086444-01

Data Table (Concise)
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