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BioAssay: AID 344874

Inhibition of ovine COX2 by enzyme immuno assay

A new class of hybrid nitric oxide-releasing anti-inflammatory (AI) ester prodrugs (NONO-coxibs 12a-b) wherein an O(2)-acetoxymethyl 1-(2-carboxypyrrolidin-1-yl)diazen-1-ium-1,2-diolate (11, O(2)-acetoxymethyl PROLI/NO) NO-donor moiety was covalently coupled to the bromomethyl group of 5-(4-bromomethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole (9a), and its methanesulfonyl more ..
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 Tested Compounds
 Tested Compounds
All(7)
 
 
Active(6)
 
 
Inconclusive(1)
 
 
 Tested Substances
 Tested Substances
All(7)
 
 
Active(6)
 
 
Inconclusive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 344874
Data Source: ChEMBL (492903)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2013-11-16

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Prostaglandin G/H synthase 2; AltName: Full=Cyclooxygenase-2; Short=COX-2; AltName: Full=PHS II; AltName: Full=Prostaglandin H2 synthase 2; Short=PGH synthase 2; Short=PGHS-2; AltName: Full=Prostaglandin-endoperoxide synthase 2; Flags: Precursor
Description ..   
Protein Family: Animal prostaglandin endoperoxide synthase and related bacterial proteins
Comment ..   

Gene:PTGS2     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 6
Description:
Title: Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-hydroxymethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole and its methanesulfonyl analog: synthesis, biological evaluation and nitric oxide release studies.

Abstract: A new class of hybrid nitric oxide-releasing anti-inflammatory (AI) ester prodrugs (NONO-coxibs 12a-b) wherein an O(2)-acetoxymethyl 1-(2-carboxypyrrolidin-1-yl)diazen-1-ium-1,2-diolate (11, O(2)-acetoxymethyl PROLI/NO) NO-donor moiety was covalently coupled to the bromomethyl group of 5-(4-bromomethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole (9a), and its methanesulfonyl analog (9b), were synthesized. The diazen-1-ium-1,2-diolate compounds 12a-b released a low amount of NO upon incubation with phosphate buffer (PBS) at pH 7.4 (6.1-8.2% range). In comparison, the percentage NO released was significantly higher (76-77% of the theoretical maximal release of two molecules of NO/molecule of the parent hybrid ester prodrug) when the diazen-1-ium-1,2-diolate ester prodrugs 12a-b were incubated in the presence of rat serum. These incubation studies suggest that both NO and the anti-inflammatory 5-(4-hydroxymethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole (10a), and its methanesulfonyl analog (10b), would be released from the parent NONO-coxib 12a or 12b upon in vivo cleavage by non-specific serum esterases. The hydroxymethyl compounds 10a-b were weak inhibitors of the cyclooxygenase-1 (COX-1) and COX-2 isozymes (IC(50)=3.7-10.5 microM range). However, the hydroxymethyl compounds 10a-b and the parent NONO-coxibs 12a-b exhibited good AI activities (ED(50)=76.7-111.6 micromol/kg po range) that were greater than that exhibited by the reference drugs aspirin (ED(50)=710 micromol/kg po) and ibuprofen (ED(50)=327 micromol/kg po), but less than that of celecoxib (ED(50)=30.9mumol/kg po). These studies indicate hybrid ester AI/NO-donor prodrugs (NONO-coxibs) constitutes a plausible drug design concept targeted toward the development of selective COX-2 inhibitory AI drugs that are devoid of adverse cardiovascular effects.
(PMID: 18930406)
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: 17100

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 binding domainsIC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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