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BioAssay: AID 621424

Inhibition of CYP3A4 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: 621424
Data Source: ChEMBL (771435)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2014-08-24

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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: 17045
Target Type: SINGLE PROTEIN
Pref Name: Cytochrome P450 3A4
Synonyms: 1;8-cineole 2-exo-monooxygenase;Albendazole monooxygenase;Albendazole sulfoxidase;CYPIIIA3;CYPIIIA4;Cytochrome P450 3A3;Cytochrome P450 3A4;Cytochrome P450 HLp;Cytochrome P450 NF-25;Cytochrome P450-PCN1;Nifedipine oxidase;Quinine 3-monooxygenase;Taurochenodeoxycholate 6-alpha-hydroxylase;
Gene Name: CYP3A3;CYP3A4;
Protein Accession: P08684;
Protein GI: 116241312;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: enzyme cytochrome p450 cyp_3 cyp_3a cyp_3a4
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: ADME
Assay Data Source: Scientific Literature
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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