Bookmark and Share
BioAssay: AID 740910

Inhibition of CYP2C19 (unknown origin)-mediated mephenytoin metabolite conversion at 10 uM after 20 mins relative to control

Recognizing acetyllysine of histone is a vital process of epigenetic regulation that is mediated by a protein module called bromodomain. To contribute novel scaffolds for developing into bromodomain inhibitors, we utilize a fragment-based drug discovery approach. By successively applying docking and X-ray crystallography, we were able to identify 9 fragment hits from diffracting more than 60 more ..
_
   
 Tested Compounds
 Tested Compounds
All(2)
 
 
Unspecified(2)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Unspecified(2)
 
 
 Related BioAssays
 Related BioAssays
AID: 740910
Data Source: ChEMBL (953478)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-11-07
Modify Date: 2014-09-05

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Cytochrome P450 2C19; AltName: Full=(R)-limonene 6-monooxygenase; AltName: Full=(S)-limonene 6-monooxygenase; AltName: Full=(S)-limonene 7-monooxygenase; AltName: Full=CYPIIC17; AltName: Full=CYPIIC19; AltName: Full=Cytochrome P450-11A; AltName: Full=Cytochrome P450-254C; AltName: Full=Mephenytoin 4-hydroxylase
Description ..   
Protein Family: Cytochrome P450
Comment ..   

Gene:CYP2C19     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Fragment-based drug discovery of 2-thiazolidinones as inhibitors of the histone reader BRD4 bromodomain.

Abstract: Recognizing acetyllysine of histone is a vital process of epigenetic regulation that is mediated by a protein module called bromodomain. To contribute novel scaffolds for developing into bromodomain inhibitors, we utilize a fragment-based drug discovery approach. By successively applying docking and X-ray crystallography, we were able to identify 9 fragment hits from diffracting more than 60 crystals. In the present work, we described four of them and carried out the integrated lead optimization for fragment 8, which bears a 2-thiazolidinone core. After several rounds of structure guided modifications, we assessed the druggability of 2-thiazolidinone by modulating in vitro pharmacokinetic studies and cellular activity assay. The results showed that two potent compounds of 2-thiazolidinones have good metabolic stability. Also, the cellular assay confirmed the activities of 2-thiazolidinones. Together, we hope the identified 2-thiazolidinone chemotype and other fragment hits described herein can stimulate researchers to develop more diversified bromodomain inhibitors.
(PMID: 23530754)
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: ADME
Target Type: Target is a single protein chain
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)
Data Table ( Complete ):     View All Data
Classification
PageFrom: