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BioAssay: AID 504643

Inhibitors of APE1: Metabolic Stability 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)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Inactive(1)
 
 
AID: 504643
Data Source: NCGC (APE1805)
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2011-04-12
Hold-until Date: 2011-05-01
Modify Date: 2011-05-03

Data Table ( Complete ):           All
Target
Tested Compound:
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)summarySummary
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 bioassays provides profiling data against mouse liver microsomes. This in vitro model is often predictive of in vivo metabolic stability by measuring the half time of the compound.

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
1uM of compound in incubated in mouse liver microsome; the reference compound is ketanserin. Compounds are incubated at 37 degrees C for different time periods: 0, 5, 15, 30, 45, and 60 minutes. Samples are analyzed with LC-MS/MS.
Comment
Compounds are "active" if half time is more than 30 minutes; "inconclusive" if half time is between 15 and 30 minutes; "inactive" if half time is less than 15 minutes.

PUBCHEM_ACTIVITY_SCORE is the whole number in minutes of T1/2 of the compound.
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Half timeT1/2 of mouse liver microsome stabilityFloatmin
2Compound QCSource of compound QCString
Additional Information
Grant Number: MH086444

Data Table (Concise)
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