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BioAssay: AID 612031

Displacement of [3H]LSD from human 5HT5A receptor at 10 uM relative to control

Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 612031
Data Source: ChEMBL (762042)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2014-05-26

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=5-hydroxytryptamine receptor 5A; Short=5-HT-5; Short=5-HT-5A; Short=5-HT5A; AltName: Full=Serotonin receptor 5A
Description ..   
Comment ..   

Gene:HTR5A     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators.

Abstract: Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan. Herein, we report a structure-activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel derivatives were synthesized, and their TDO inhibitory potency was evaluated. The rationalization of the structure-activity relationships (SARs) revealed essential features to attain high TDO inhibition and notably a dense H-bond network mainly involving His(55) and Thr(254) residues. Our study led to the identification of a very promising compound (58) displaying good TDO inhibition (K(i) = 5.5 muM), high selectivity, and good oral bioavailability. Indeed, 58 was chosen for preclinical evaluation.
(PMID: 21726069)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Target Type: Target is a single protein chain

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)
Classification
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