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BioAssay: AID 1548

Summary assay for compounds activating TNAP performed in a luminescent assay

Assay Providers: Drs. Jose Luis Millan and Eduard Sergienko, Sanford-Burnham Medical Research Institute, San Diego, CA. ..more
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 Tested Compounds
 Tested Compounds
All(2)
 
 
Probe(2)
 
 
Active(2)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Probe(2)
 
 
Active(2)
 
 
AID: 1548
Data Source: Burnham Center for Chemical Genomics (BCCG-A148-TNAP_Activator_Summary_Assay)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Screening Center Network
BioAssay Version:
Deposit Date: 2009-03-12
Modify Date: 2010-12-30

Data Table ( Complete ):           View Active Data    View All Data
Target
BioActive Compounds: Chemical Probe: 2    Active: 2
Related Experiments
Show more
AIDNameTypeComment
518TNAP luminescent HTS assayConfirmatorydepositor-specified cross reference: TNAP luminescent HTS assay
813HTS identification of compounds activating TNAP at intermediate concentration of phosphate acceptor detected in luminescent assayScreeningdepositor-specified cross reference: HTS identification of compounds activating TNAP at intermediate concentration of phosphate acceptor
1001uHTS identification of compounds activating TNAP in the absence of phosphate acceptor performed in luminescent assayConfirmatorydepositor-specified cross reference: uHTS identification of compounds activating TNAP in the absence of phosphate acceptor performed in l
1056SAR analysis of an In Vitro TNAP Dose Response Luminescent AssayConfirmatorydepositor-specified cross reference
1136uHTS identification of compounds activating TNAP at a high concentration of phosphate acceptor detected in a luminescent assayScreeningdepositor-specified cross reference: uHTS identification of compounds activating TNAP at a high concentration of phosphate acceptor detec
1227GAPDH Dose Response Colorimetric AssayConfirmatorydepositor-specified cross reference: GAPDH Dose Response Colorimetric Assay
1450SAR assay for compounds activating TNAP in the absence of phosphate acceptor performed in a luminescent assayConfirmatorydepositor-specified cross reference: SAR assay for compounds activating TNAP in the absence of phosphate acceptor performed in a luminesc
1659SAR assay for compounds activating TNAP in the presence of 100 mM DEA performed in a luminescence assayConfirmatorydepositor-specified cross reference: SAR assay for compounds activating TNAP in the presence of 100 mM DEA performed in a luminescence as
1941SAR assay for compounds inhibiting TNAP in the absence of phosphate acceptor performed in a luminescent assayConfirmatorydepositor-specified cross reference
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Screening Centers Network (MLSCN)
Grant Proposal Number: 1R03 MH082385-01
Assay Providers: Drs. Jose Luis Millan and Eduard Sergienko, Sanford-Burnham Medical Research Institute, San Diego, CA.

Alkaline phosphatases (EC 3.1.3.1) (APs) catalyze the hydrolysis of phosphomonoesters, releasing phosphate and alcohol. APs are dimeric enzymes found in the most organisms. In human, four isozymes of APs have been identified. Three isozymes are tissue-specific and the fourth one is tissue-non specific, named TNAP. TNAP deficiency is associated with defective bone mineralization in the form of rickets and osteomalacia. Therefore, there is therapeutic potential of modulating TNAP activity.

The goal of this HTS is to identify novel and specific activators of TNAP. The only known to date class of alkaline phosphatases activators are amino-containing alcohols, such as diethanolamine (DEA), that act as phosphoacceptor substrate and exhibit its effect in high-mM concentration range. Compounds with a similar mode of action are expected to demonstrate diminished stimulating potential if tested in the presence of DEA. Therefore, for detection of compounds with diverse mode of action, the HTS assay was optimized and HTS campaigns were performed in the presence and in the absence of DEA. The current AID reports a set of the data from screening in the absence of DEA or any other phosphate acceptor.

AIDs 518, 813, 1001, 1136, 1227, 1450 and 1659 were carried out to select probe molecules SID48410176(ML088) and SID56373763(ML087).
Protocol
Please see pertinent AIDs: 518, 813, 1001, 1136, 1227, 1450, 1659
Comment
This AID is used to summarize the results of this MLPCN project. Probe molecules are defined as the positives of this assay and assigned a score of 100
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 2
MLP Probe ML# for probe 1: ML088
PubChem Substance ID (SID) for probe 1: 48410176
PubChem Compound ID (CID) for probe 1: 704205
Probe type for probe 1: Activator
IC50/EC50 (nM) for probe 1: 6190
Target for probe 1: TNAP (gi: 116734717)
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK47339/ (ID: 2358390)
Grant number for probe 1: MH082385-01
MLP Probe ML# for probe 2: ML087
PubChem Substance ID (SID) for probe 2: 56373763
PubChem Compound ID (CID) for probe 2: 25199559
Probe type for probe 2: Activator
IC50/EC50 (nM) for probe 2: 199
Target for probe 2: TNAP (gi: 116734717)
NCBI Book chapter title for probe 1: HTS identification of compounds activating TNAP at an intermediate concentration of phosphate acceptor detected in luminescent assay
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1ML#ML# of the compoundString
Additional Information
Grant Number: 1R03 MH082385-01

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
Classification
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