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BioAssay: AID 618496

Inhibition of G9a in human PC3 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay

Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most potent G9a inhibitor to date, via structure-based design and structure-activity more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Active(3)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Active(3)
 
 
AID: 618496
Data Source: ChEMBL (768507)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2014-08-24

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Histone-lysine N-methyltransferase EHMT2; AltName: Full=Euchromatic histone-lysine N-methyltransferase 2; AltName: Full=HLA-B-associated transcript 8; AltName: Full=Histone H3-K9 methyltransferase 3; Short=H3-K9-HMTase 3; AltName: Full=Lysine N-methyltransferase 1C; AltName: Full=Protein G9a
Description ..   
Protein Family: SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
Comment ..   

Gene:EHMT2     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 3
Description:
Title: Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy-quinazolines.

Abstract: Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most potent G9a inhibitor to date, via structure-based design and structure-activity relationship (SAR) exploration of the quinazoline scaffold represented by BIX01294 (1). Despite its very high in vitro potency, compound 3 lacks sufficient cellular potency. The design and synthesis of several generations of new analogues aimed at improving cell membrane permeability while maintaining high in vitro potency resulted in the discovery of a number of novel G9a inhibitors such as UNC0646 (6) and UNC0631 (7) with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity. The design, synthesis, and cellular SAR of these potent G9a inhibitors are described.
(PMID: 21780790)
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
BAO: Assay Format: cell-based format
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloatμM
10IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

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