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BioAssay: AID 411273

Inhibition of human recombinant Gcn5 assessed as reduction in acetylated histone H3 level at 0.2 mM by Western blot analysis

Acetylation is a key modulator of genome accessibility through decondensation of the chromatin structure. The balance between acetylation and opposite deacetylation is, in fact, a prerequisite for several cell functions and differentiation. To find modulators of the histone acetyltransferase Gcn5p, we performed a phenotypic screening on a set of newly synthesized molecules derived from thiazole more ..
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 Tested Compounds
 Tested Compounds
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Active(1)
 
 
 Tested Substances
 Tested Substances
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Active(1)
 
 
AID: 411273
Data Source: ChEMBL (559302)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2014-05-26

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Histone acetyltransferase KAT2A; AltName: Full=General control of amino acid synthesis protein 5-like 2; AltName: Full=Histone acetyltransferase GCN5; Short=HsGCN5; AltName: Full=Lysine acetyltransferase 2A; AltName: Full=STAF97
Description ..   
Protein Family: PCAF (P300/CBP-associated factor) N-terminal domain
Comment ..   

Gene:KAT2A     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: A novel histone acetyltransferase inhibitor modulating Gcn5 network: cyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl)hydrazone.

Abstract: Acetylation is a key modulator of genome accessibility through decondensation of the chromatin structure. The balance between acetylation and opposite deacetylation is, in fact, a prerequisite for several cell functions and differentiation. To find modulators of the histone acetyltransferase Gcn5p, we performed a phenotypic screening on a set of newly synthesized molecules derived from thiazole in budding yeast Saccharomyces cerevisiae. We selected compounds that induce growth inhibition in yeast strains deleted in genes encoding known histone acetyltransferases. A novel molecule CPTH2, cyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl)hydrazone, was selected based on its inhibitory effect on the growth of a gcn5Delta strain. We demonstrated a specific chemical-genetic interaction between CPTH2 and HAT Gcn5p, indicating that CPTH2 inhibits the Gcn5p dependent functional network. CPTH2 inhibited an in vitro HAT reaction, which is reverted by increasing concentration of histone H3. In vivo, it decreased acetylation of bulk histone H3 at the specific H3-AcK14 site. On the whole, our results demonstrate that CPTH2 is a novel HAT inhibitor modulating Gcn5p network in vitro and in vivo.
(PMID: 19099397)
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
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat
5Activity standard valueActivity standard valueFloat

Data Table (Concise)
Classification
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