Bookmark and Share
BioAssay: AID 646028

Inhibition of human COX-2-mediated PGE2 production after 24 hrs

Bromodomain-containing proteins are key epigenetic regulators of gene transcription and readers of the histone code. However, the therapeutic benefits of modulating this target class are largely unexplored due to the lack of suitable chemical probes. This article describes the generation of lead molecules for the BET bromodomains through screening a fragment set chosen using structural insights more ..
_
   
 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
AID: 646028
Data Source: ChEMBL (803476)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-24

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Prostaglandin G/H synthase 2; AltName: Full=Cyclooxygenase-2; Short=COX-2; AltName: Full=PHS II; AltName: Full=Prostaglandin H2 synthase 2; Short=PGH synthase 2; Short=PGHS-2; AltName: Full=Prostaglandin-endoperoxide synthase 2; Flags: Precursor
Description ..   
Protein Family: Animal prostaglandin endoperoxide synthase and related bacterial proteins
Comment ..   

Gene:PTGS2     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Fragment-based discovery of bromodomain inhibitors part 1: inhibitor binding modes and implications for lead discovery.

Abstract: Bromodomain-containing proteins are key epigenetic regulators of gene transcription and readers of the histone code. However, the therapeutic benefits of modulating this target class are largely unexplored due to the lack of suitable chemical probes. This article describes the generation of lead molecules for the BET bromodomains through screening a fragment set chosen using structural insights and computational approaches. Analysis of 40 BRD2/fragment X-ray complexes highlights both shared and disparate interaction features that may be exploited for affinity and selectivity. Six representative crystal structures are then exemplified in detail. Two of the fragments are completely new bromodomain chemotypes, and three have never before been crystallized in a bromodomain, so our results significantly extend the limited public knowledge-base of crystallographic small molecule/bromodomain interactions. Certain fragments (including paracetamol) bind in a consistent mode to different bromodomains such as CREBBP, suggesting their potential to act as generic bromodomain templates. An important implication is that the bromodomains are not only a phylogenetic family but also a system in which chemical and structural knowledge of one bromodomain gives insights transferrable to others.
(PMID: 22136404)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
Protein Target Class: enzyme reductase
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1INH activity commentINH activity commentString
2INH standard flagINH standard flagInteger
3INH qualifierINH qualifierString
4INH published valueINH published valueFloatμM
5INH standard valueINH standard valueFloatμM

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
PageFrom: