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BioAssay: AID 621423

Inhibition of CYP2D6 at 10 uM

The pyrrole based N6022 was recently identified as a potent, selective, reversible, and efficacious S-nitrosoglutathione reductase (GSNOR) inhibitor and is currently undergoing clinical development for the treatment of acute asthma. GSNOR is a member of the alcohol dehydrogenase family (ADH) and regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO). more ..
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 Tested Compounds
 Tested Compounds
All(6)
 
 
Unspecified(6)
 
 
 Tested Substances
 Tested Substances
All(6)
 
 
Unspecified(6)
 
 
 Related BioAssays
 Related BioAssays
AID: 621423
Data Source: ChEMBL (771434)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2014-05-26

Data Table ( Complete ):           View All Data
Tested Compounds:
Description:
Title: Discovery of potent and novel S-nitrosoglutathione reductase inhibitors devoid of cytochrome P450 activities.

Abstract: The pyrrole based N6022 was recently identified as a potent, selective, reversible, and efficacious S-nitrosoglutathione reductase (GSNOR) inhibitor and is currently undergoing clinical development for the treatment of acute asthma. GSNOR is a member of the alcohol dehydrogenase family (ADH) and regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO). Reduced levels of GSNO, as well as other nitrosothiols (SNOs), have been implicated in the pathogenesis of many diseases including those of the respiratory, cardiovascular, and gastrointestinal systems. Preservation of endogenous SNOs through GSNOR inhibition presents a novel therapeutic approach with broad applicability. We describe here the synthesis and structure-activity relationships (SAR) of novel pyrrole based analogues of N6022 focusing on removal of cytochrome P450 inhibition activities. We identified potent and novel GSNOR inhibitors having reduced CYP inhibition activities and demonstrated efficacy in a mouse ovalbumin (OVA) model of asthma.
(PMID: 21855338)
Comment
Putative Target:

ChEMBL Target ID: 11365
Target Type: SINGLE PROTEIN
Pref Name: Cytochrome P450 2D6
Synonyms: CYPIID6;Cytochrome P450 2D6;Cytochrome P450-DB1;Debrisoquine 4-hydroxylase;
Gene Name: CYP2D6;CYP2DL1;
Protein Accession: P10635;
Protein GI: 84028191;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: enzyme cytochrome p450 cyp_2 cyp_2d cyp_2d6
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment
Assay Type: ADME

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Inhibition activity commentInhibition activity commentString
2Inhibition standard flagInhibition standard flagInteger
3Inhibition qualifierInhibition qualifierString
4Inhibition published valueInhibition published valueFloat%
5Inhibition standard valueInhibition standard valueFloat%

Data Table (Concise)
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