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BioAssay: AID 219559

Inhibition of bovine adrenal cholesterol side chain cleavage(CSCC) cytochrome P450 11A1

In exploring the structural features responsible for the inhibitory activity of aminoglutethimide [3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione] (1) toward the cholesterol side chain cleavage (CSCC) enzyme from bovine adrenals and the human placental aromatase enzyme, analogues have been synthesized in which the piperidine-2,6-dione ring is replaced by substituted or unsubstituted more ..
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 Tested Compounds
 Tested Compounds
All(13)
 
 
Active(1)
 
 
Unspecified(12)
 
 
 Tested Substances
 Tested Substances
All(13)
 
 
Active(1)
 
 
Unspecified(12)
 
 
AID: 219559
Data Source: ChEMBL (216898)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-21
Modify Date: 2014-05-20

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Cholesterol side-chain cleavage enzyme, mitochondrial; AltName: Full=CYPXIA1; AltName: Full=Cholesterol desmolase; AltName: Full=Cytochrome P450 11A1; AltName: Full=Cytochrome P450(scc); Flags: Precursor
Description ..   
Protein Family: Cytochrome P450
Comment ..   

Gene:CYP11A1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Analogues of aminoglutethimide based on 1-phenyl-3-azabicyclo[3.1.0]hexane-2,4-dione: selective inhibition of aromatase activity.

Abstract: In exploring the structural features responsible for the inhibitory activity of aminoglutethimide [3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione] (1) toward the cholesterol side chain cleavage (CSCC) enzyme from bovine adrenals and the human placental aromatase enzyme, analogues have been synthesized in which the piperidine-2,6-dione ring is replaced by substituted or unsubstituted azabicyclo[3.1.0]hexane-2,4-dione rings. The unsubstituted analogue 1-(4-aminophenyl)-3-azabicyclo[3.1.0]hexane-2,4-dione (9a) is a slightly more potent inhibitor of aromatase than 1 (Ki = 1.2 microM, cf. 1.8 microM for 1) but is noninhibitory toward the CSCC enzyme. The substituted analogues 1-(4-aminophenyl)-3-butyl-3-azabicyclo[3.1.0]hexane-2,4-dione (9e) and 1-(4-aminophenyl)-3-pentyl-3-azabicyclo[3.1.0]hexane-2,4-dione (9f) are approximately 100 times more potent than 1 (Ki values of 1, 9e, and 9f are 1.8, 0.015, and 0.02 microM, respectively) in inhibiting aromatase, with no significant activity toward the CSCC enzyme. Type II difference spectra were exhibited by 1, 9a, and 9f in their interaction with the aromatase enzyme (respective Ks values of 1, 9a, and 9f are 0.13, 0.08, and 0.01 microM). Modification of the para amino function by alkylation, its relocation, replacement by H, or replacement by a methyl, aldehyde, or secondary alcohol group produced analogues that were inactive toward both enzyme systems.
(PMID: 3361583)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

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
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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
11IC50 data validityIC50 data validityString
12IC50 binding domainsIC50 binding domainsString

* Activity Concentration.

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