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BioAssay: AID 494634

Inhibition of sheep COX1 by enzyme immunoassay

A new class of anti-inflammatory (AI) cupferron prodrugs was synthesized wherein a diazen-1-ium-1,2-diolato ammonium salt, and its O(2)-methyl and O(2)-acetoxyethyl derivatives, nitric oxide (NO) donor moieties were attached directly to an aryl carbon on a celecoxib template. The percentage of NO released from the O(2)-methyl and O(2)-acetoxyethyl compounds was higher (18.0-37.8% of the more ..
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 Tested Compounds
 Tested Compounds
All(8)
 
 
Active(7)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(8)
 
 
Active(7)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 494634
Data Source: ChEMBL (644674)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-02-25
Modify Date: 2013-11-16

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Prostaglandin G/H synthase 1; AltName: Full=Cyclooxygenase-1; Short=COX-1; AltName: Full=Prostaglandin H2 synthase 1; Short=PGH synthase 1; Short=PGHS-1; Short=PHS 1; AltName: Full=Prostaglandin-endoperoxide synthase 1; Flags: Precursor
Description ..   
Protein Family: Animal prostaglandin endoperoxide synthase and related bacterial proteins
Comment ..   

Gene:PTGS1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 7
Description:
Title: Celecoxib prodrugs possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: synthesis, biological evaluation and nitric oxide release studies.

Abstract: A new class of anti-inflammatory (AI) cupferron prodrugs was synthesized wherein a diazen-1-ium-1,2-diolato ammonium salt, and its O(2)-methyl and O(2)-acetoxyethyl derivatives, nitric oxide (NO) donor moieties were attached directly to an aryl carbon on a celecoxib template. The percentage of NO released from the O(2)-methyl and O(2)-acetoxyethyl compounds was higher (18.0-37.8% of the theoretical maximal release of one molecule of NO/molecule of the parent compound) upon incubation in the presence of rat serum, relative to incubation with phosphate buffer saline (PBS) at pH 7.4 (3.8-11.6% range). All compounds exhibited weak inhibition of the COX-1 isozyme (IC(50)=5.8-17.0 microM range) in conjunction with weak or modest inhibition of the COX-2 isozyme (IC(50)=1.6-14.4 microM range). The most potent AI agent 5-[4-(O(2)-ammonium diazen-1-ium-1,2-diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole exhibited a potency that was about fourfold and twofold greater than that observed for the respective reference drugs aspirin and ibuprofen. These studies indicate that use of a cupferron template constitutes a plausible drug design approach targeted toward the development of AI drugs that do not cause gastric irritation, or elevate blood pressure and induce platelet aggregation that have been associated with the use of some selective COX-2 inhibitors.
(PMID: 20576432)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 17047

ChEMBL Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloatμM
10IC50 standard valueIC50 standard valueFloatnM
11IC50 data validityIC50 data validityString
12IC50 binding domainsIC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
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