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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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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 ):           View Active Data    View All Data
BioActive Compound: 1
Related Experiments
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AIDNameTypeComment
2386Probe Development Summary for Inhibitors of Bloom's syndrome helicase (BLM)Summarydepositor-specified cross reference: Summary AID
2364qHTS Validation Assay for Inhibitors of Bloom's syndrome helicase (BLM)Confirmatorysame project related to Summary assay
2528qHTS Assay for Inhibitors of Bloom's syndrome helicase (BLM)Confirmatorysame project related to Summary assay
2585qHTS Confirmation Assay for Inhibitors of Bloom's syndrome helicase (BLM)Confirmatorysame project related to Summary assay
2712Counterscreen for BLMA Inhibitors: ADP Fluorescence Polarization Displacement AssayConfirmatorysame project related to Summary assay
504662Inhibitors of BLM Helicase: DNA Unwinding Measured by Gel Electrophoresis - BLM Helicase ActivityConfirmatorysame project related to Summary assay
504663Inhibitors of BLM Helicase: DNA Unwinding Measured by Gel Electrophoresis - RecQL1 Helicase CounterscreenConfirmatorysame project related to Summary assay
504736Inhibitors of Bloom's syndrome helicase: Efflux Ratio Profiling AssayOthersame project related to Summary assay
504737Inhibitors of Bloom's syndrome helicase: Caco-2 Permeability Profiling AssayOthersame project related to Summary assay
504738Inhibitors of Bloom's syndrome helicase: Aqueous Profiling AssayOthersame project related to Summary assay
504740Inhibitors of Bloom's syndrome helicase: Mouse Plasma Stability ProfilingOthersame project related to Summary assay
504741Inhibitors of Bloom's syndrome helicase: PBS Stability Profiling AssayOthersame project related to Summary assay
720549qHTS for Inhibitors of Bloom's syndrome helicase (BLM): Helicase ATPase Orthogonal Confirmatory Assay for SAROthersame project related to Summary assay
720550qHTS for Inhibitors of Bloom's syndrome helicase (BLM): Thiazole Orange DNA Binding Counterscreen for SAR.Othersame project related to Summary assay
720555qHTS for Inhibitors of Bloom's syndrome helicase (BLM): Helicase DNA unwinding fluorescent orthogonal confirmatory assay for SAROthersame project related to Summary assay
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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