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BioAssay: AID 639952

Inhibition of TNF-alpha-induced NF-kappaB activation in human HCT116 cells at 1 mM after 6 hrs by luciferase reporter gene assay

To develop a more potent NFkappaB inhibitor from salicylic acid which is known to inhibit activity of NFkappaB, a transcription factor regulating genes involved in immunity, inflammation and tumorigenesis, derivatives of salicylic acid (SA) where the 5 position, carboxyl or hydroxyl group was modified were treated in HCT116 cells transfected with an NFkappaB dependent luciferase gene and more ..
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 Tested Compounds
 Tested Compounds
All(8)
 
 
Active(8)
 
 
 Tested Substances
 Tested Substances
All(8)
 
 
Active(8)
 
 
 Related BioAssays
 Related BioAssays
AID: 639952
Data Source: ChEMBL (797400)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-25

Data Table ( Complete ):           Active    All
BioActive Compounds: 8
Description:
Title: Structure-activity relationship of salicylic acid derivatives on inhibition of TNF-alpha dependent NFkappaB activity: Implication on anti-inflammatory effect of N-(5-chlorosalicyloyl)phenethylamine against experimental colitis.

Abstract: To develop a more potent NFkappaB inhibitor from salicylic acid which is known to inhibit activity of NFkappaB, a transcription factor regulating genes involved in immunity, inflammation and tumorigenesis, derivatives of salicylic acid (SA) where the 5 position, carboxyl or hydroxyl group was modified were treated in HCT116 cells transfected with an NFkappaB dependent luciferase gene and LPS-stimulated RAW264.7 cells. Amidation of the carboxylic group or substitution of chlorine at the 5 position increased the ability of SA to suppress the expression of NFkappaB dependent luciferase and inducible nitric oxide synthase, a product of an NFkappaB target gene. Moreover, simultaneous amidation and chlorination of SA (5-chlorosalicylamide; 5-CSAM) conferred an additive NFkappaB inhibitory activity on SA. To further enhance the inhibitory activity, N-modification was imposed on 5-CSAM. N-(5-chlorosalicyloyl)phenethylamine (5-CSPA), N-(5-chlorosalicyloyl)3-phenylpropylamine (5-CSPPA) and N-(5-chlorosalicyloyl)4-hydroxyphenylethylamine (5-CSHPA) showed greater potencies for inhibiting NFkappaB activity than other derivatives. Their IC(50)s' in the luciferase assay measured 15muM (5-CSPA), 17muM (5-CSPPA) and 91muM (5-CSHPA). Rectal administration of 5-CSPA ameliorated TNBS-induced rat colitis, which was more effective than a conventional drug, 5-aminosalicylic acid. These data may provide useful information for development of a therapeutic agent for treatment of diseases where NFkappaB plays a critical role in the pathogenic progresses.
(PMID: 22154834)
Comment
Putative Target:

ChEMBL Target ID: 22226
Target Type: UNCHECKED
Pref Name: Unchecked
Confidence: Default value - Target unknown or has yet to be assigned
Relationship Type: Default value - Target has yet to be curated
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based 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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