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BioAssay: AID 504739

Inhibitors of Bloom's syndrome helicase: Metabolic Stability Profiling

Survival of cells and the faithful propagation of the genome depend on elaborate mechanisms of detecting and repairing DNA damage. Treatment of advanced cancer relies on radiation therapy or chemotherapy, which kill cancer cells by causing extensive DNA damage. It is often found, that cancer cells develop resistance to therapy through enhanced activity of DNA repair functions; this has led to an more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 504739
Data Source: NCGC (BLMA604)
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2011-05-09
Hold-until Date: 2012-05-06
Modify Date: 2012-05-08

Data Table ( Complete ):           Active    All
BioActive Compound: 1
Depositor Specified Assays
AIDNameTypeComment
2386Probe Development Summary for Inhibitors of Bloom's syndrome helicase (BLM)summarySummary AID
Description:
Survival of cells and the faithful propagation of the genome depend on elaborate mechanisms of detecting and repairing DNA damage. Treatment of advanced cancer relies on radiation therapy or chemotherapy, which kill cancer cells by causing extensive DNA damage. It is often found, that cancer cells develop resistance to therapy through enhanced activity of DNA repair functions; this has led to an increased interest in developing drugs that interfere with DNA repair, which could sensitize cancer cells to conventional therapy. Bloom syndrome helicase (BLM), is important in resolving abnormal DNA structures formed during replication or homologous recombination. Shutting down the expression of BLM leads to chromosomal instability and higher radiation sensitivity in cultured cells. After the completion of a qHTS campaign, secondary assays, and rounds of medicinal chemistry, a compound was identified to be further characterized through in vitro ADME assays.

Mouse liver microsomes are created through broken up endoplasmic reticulum from mouse liver. These liver microsomes contain many drug metabolizing enzymes, such as Cytochome P-450s and flavin-containing monooxygenases. Because metabolism is major way of drug clearance, this is an important result.

NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Production Centers Network [MLPCN]

MLSCN Grant: MH087284
PI Name: Dr. Opher Gileadi, Structural Genomics Consortium, University of Oxford, UK
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 TimeMouse liver microsome stability (T1/2)Floatmin
2Compound QCSource of compound QCString
Additional Information
Grant Number: MH087284

Data Table (Concise)
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